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BACKGROUND: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program. METHODS: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications. RESULTS: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P

BACKGROUND: Validating the National Institutes of Health NIH Stroke Scale (NIHSS) as a tool to assess deficit severity and prognosis in patients with acute intracerebral hemorrhage would harmonize the assessment of intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) patients, enable clinical use of a readily implementable and non-imaging dependent prognostic tool, and improve monitoring of ICH care quality in administrative datasets. METHODS: Among randomized trial ICH patients, the relation between NIHSS scores early after Emergency Department arrival and 3-month outcomes of dependency or death (modified Rankin Scale, mRS 3-6) and case fatality was examined. NIHSS predictive performance was compared to a current standard prognostic scale, the intracerebral hemorrhage score (ICH score). RESULTS: Among the 384 patients, the mean age was 65 (±13), with 66% being male. The median NIHSS score was 16 (interquartile range (IQR) 9-25), the mean initial hematoma volume was 29 mL (±38), and the ICH score median was 1 (IQR 0-2). At 3 months, the mRS had a median of 4 (IQR 2-6), with dependency or death occurring in 70% and case fatality in 26%. The NIHSS and ICH scores were strongly correlated (r = 0.73), and each was strongly correlated with the 90-day mRS (NIHSS, r = 0.61; ICH score, r = 0.62). The NIHSS performed comparably to the ICH score in predicting both dependency or death (c = 0.80 vs. 0.80, p = 0.83) and case fatality (c = 0.78 vs. 0.80, p = 0.29). At threshold values, the NIHSS predicted dependency or death with 74.1% accuracy (NIHSS 17.5) and case fatality with 75.0% accuracy (NIHSS 18.5). CONCLUSION: The NIHSS forecasts 3-month functional and case fatality outcomes with accuracy comparable to the ICH Score. Widely documented in routine clinical care and administrative data, the NIHSS can serve as a valuable measure for clinical prognostication, therapy development, and case-mix risk adjustment in ICH patients.Clinical trial registrationClinicaltrials.gov, NCT00059332.

Background: End stage renal disease (ESRD) requiring hemodialysis (HD) increases mortality among patients with intracerebral hemorrhage (ICH). The aim of this study is to investigate the clinical characteristics and outcome of ICH patients with ESRD on HD versus propensity-score matched controls. Methods: This is a single center retrospective study. Consecutive ICH admissions at the University of California, Irvine Medical Center from January 1, 2018 to July 31, 2022 were analyzed. Results: Among 347 ICH admissions that met inclusion criteria, 24 patients (6.92%) had ESRD on HD. Compared to patients without ESRD, patients with ESRD on HD had significantly higher rate of diabetes mellitus (79.2% vs. 36.8%, p < 0.01) and in-hospital mortality (25% vs. 7.43%, p < 0.01). There were no significant differences in demographics, other comorbidities, clinical characteristics, good (mRS score 0–3) or poor (mRS score 4–5) functional outcomes, rate of comfort care and the time to comfort care decision between the 2 groups. After propensity score matching, the ESRD group had a significantly higher in-hospital mortality rate (27.3% vs. 8%, p = 0.012) and a lower rate of obesity (9.1% vs. 34.1%, p = 0.02). Among patients who died during admission, ESRD on HD status did not inadvertently influence end-of-life care decisions. Univariate logistic regression and area under curve analysis showed that ICH score ≥ 3 was a predictor of increased mortality in both ESRD and non-ESRD groups. Conclusions: ICH patients with ESRD on HD had significantly higher in-hospital mortality and lower rate of obesity than propensity score matched controls, suggesting a survival benefit from obesity. ICH score ≥ 3 is an independent predictor for poor outcomes in both ESRD and non-ESRD groups. [ABSTRACT FROM AUTHOR]

Acute hydrocephalus is a severe complication that may occur early after an intracerebral hemorrhage (ICH). However, clinical factors predicting the occurrence of acute hydrocephalus have rarely been studied. This study aimed to establish a nomogram model to predict early acute hydrocephalus after ICH. We retrospectively analyzed the data of 930 patients with ICH who were treated at our hospital between January 2017 and May 2024. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen for risk factors for acute hydrocephalus, and stepwise logistic regression analysis was used to construct the prediction model, which was visualized using a nomogram. Data were randomly divided into training (n = 652) and test (n = 278) sets at a 7:3 ratio. A total of 930 patients were included, of whom 123 (13.2%) developed acute hydrocephalus within 6 h of being diagnosed with ICH. Univariate analysis revealed that 11 indicators were associated with acute hydrocephalus. In the training set, LASSO and stepwise logistic regression analyses identified four independent risk factors that were used to establish a prediction model. These were the modified Graeb score, age, infratentorial hemorrhage > 15 mL, and thalamic hemorrhage > 15 mL. A graphical nomogram was then developed. The area under the receiver operating characteristic (ROC) curve was 0.974 (95% confidence interval 0.961–0.987). In the Hosmer–Lemeshow test, the p-value was 0.887. The mean absolute error of the calibration plot was 0.012. The decision curve analysis (DCA) validated the fitness and clinical application value of this nomogram. Internal validation showed the test set was in good accordance with the training set. The nomogram prediction model showed good accuracy and could be used to predict the risk of early acute hydrocephalus after ICH, thereby aiding neurologist in making rapid clinical decisions. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Affective disturbances and cognitive impairment are common sequelae of intracerebral hemorrhage (ICH), yet predictive models for these outcomes remain limited, especially for spontaneous supratentorial ICH with small hematomas (<30 mL). The aim of this study was to investigate predictors of affective disturbances and cognitive impairment following small spontaneous supratentorial intracerebral hemorrhage.We retrospectively analyzed 1692 patients with spontaneous supratentorial ICH between January 2018 and December 2020 at the First Affiliated Hospital of Harbin Medical University. Of these, 1563 patients completed a median follow‐up of 3.5 years. Cognitive function was evaluated using the modified Telephone Interview for Cognitive Status, and affective disturbances using the Hamilton Depression Scale and the Hamilton Anxiety Scale. Restricted cubic spline analyses were employed to examine the relationships between predictors and outcomes.In this cohort, 58.5% had cognitive impairment, 52.8% reported depressive symptoms, and 39.4% exhibited anxiety symptoms. Logistic regression models using Boruta's algorithm demonstrated strong predictive capacity, with areas under the curve of 0.82 for cognitive impairment, 0.78 for depressive symptoms, and 0.73 for anxiety symptoms. Hematoma volume was significantly linked to depressive symptoms (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.38–1.76) and inversely to cognitive impairment (OR 0.67, 95% CI 0.59–0.77). Uric acid levels displayed a nonlinear relationship with cognitive impairment (OR 0.70, 95% CI 0.61–0.81). Hospitalization days significantly raised the risk of both depressive (OR 1.16, 95% CI 1.03–1.30) and anxiety symptoms (OR 1.17, 95% CI 1.04–1.31).The logistic regression model, enhanced by Boruta's algorithm, provides a valuable tool for predicting affective disturbances and cognitive impairment after ICH. It facilitates early identification and improves risk assessment for these neuropsychiatric outcomes in patients with small hematomas. [ABSTRACT FROM AUTHOR]

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Introduction: Ferroptosis is a crucial process contributing to neuronal damage following intracerebral hemorrhage (ICH). Didang Tang (DDT), a traditional therapeutic, has been used clinically to manage ICH for many years, yet the molecular mechanisms by which by DDT protects neurons from ferroptosis after ICH remain elusive. Methods: This study utilized high-performance liquid chromatography-based fingerprint analysis to characterize DDT's chemical composition. An ICH rat model and hemin and erastin-induced PC12 cell ferroptosis models were developed to investigate DDT's neuroprotective mechanisms. Histological assessments of brain tissue morphology and iron deposition were performed using hematoxylin-eosin, Nissl, and Perl's blue staining. Neurological function was evaluated using Longa and Berderson scores, while lipid peroxidation was measured using biochemical assays and flow cytometry. Protein expression levels of ferroptosis- and endoplasmic reticulum stress (ERS)-related markers were analyzed via Western blotting and immunofluorescence. Results: Our results demonstrated that DDT reduced hematoma volume, decreased iron deposition, lowered malondialdehyde (MDA) levels, and upregulated glutathione peroxidase (GPX4) and SLC7A11 expression in affected brain regions. Furthermore, DDT downregulated GRP78 expression and inhibited the PERK/eIF2α/ATF4/CHOP/GPX4 pathway, exerting strong neuroprotective effects. The fluorescence staining results of MAP2/GPX4 and MAP2/CHOP suggested that DDT may regulate neuronal ferroptosis and ERs to exert the protective effect. In vitro experiments using hemin- and erastin-induced neuron-derived PC12 cells as neuronal ferroptosis models developed in our laboratory corroborated these in vivo findings, showing increased survival and reduced lipid peroxidation in DDT-treated cells, along with similar inhibitory effects on ferroptosis and ERS. Molecular docking suggested that DDT components, such as sennoside B, amygdalin, rhein, and emodin, interact favorably with PERK/eIF2α/ATF4/CHOP signaling pathway proteins, highlighting their potential role in DDT's anti-ferroptosis effects. Conclusion: DDT alleviates neuronal ferroptosis after ICH by modulating the PERK/eIF2α/ATF4/CHOP/GPX4 signaling pathway. Overall, this study provides novel insights into DDT's protective mechanisms against ICH-induced neuronal injury by modulating ferroptosis and ERS pathways, underscoring its potential as an effective therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common neurosurgical emergency with high morbidity and mortality. The trans-sylvian microsurgical evacuation of ICH in the basal ganglia is a classic but technically challenging approach. Method: We describe a novel technique using handheld portable ultrasound to guide trans-sylvian, trans-insular evacuation of basal ganglia hematomas, allowing for rapid identification, precise evacuation, and post-evacuation assessment from a small Sylvian fissure opening. Conclusion: Intraoperative portable ultrasonography is a rapid, simple, and inexpensive technique that provides real-time visualization of ICH and key cortical structures, minimizing potential damage during exposure and exploration. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. METHODS: We included Dutch‐type hereditary CAA (D‐CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age‐matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI‐cSVD burden and cognition. RESULTS: D‐CAA ICH− mutation carriers exhibited poorer global cognition and executive function compared to age‐matched controls. Patients with sCAA performed worse across all cognitive domains compared to D‐CAA ICH+ mutation carriers and age‐matched controls. MRI‐cSVD burden is associated with decreased processing speed. DISCUSSION: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI‐cSVD burden being associated with slower processing speed. Highlights: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH).Presymptomatic Dutch‐type CAA (D‐CAA) mutation carriers show worse cognition than age‐matched controls.More early awareness of cognitive dysfunction in CAA before first sICH is needed.Increased cerebral small vessel disease CAA‐burden on magnetic resonance imaging is linked to a decrease in processing speed. [ABSTRACT FROM AUTHOR]

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24 h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications. [ABSTRACT FROM AUTHOR]

Introduction: The subarachnoid space in the brain contains crucial blood vessels and cerebrospinal fluid. Aneurysms in these vessels can lead to subarachnoid hemorrhage (SAH), a serious stroke subtype with high morbidity and mortality rates. SAH treatment includes procedures like coiling and clipping, but these are available only at comprehensive stroke centers (CSCs), necessitating urgent diagnosis and transfer to specialized facilities. Methods: This IRB-approved study was conducted by Polk County Fire Rescue (PCFR) in Florida. PCFR, serving an 850,000-person population, implemented a three-step SAH protocol. The protocol uses both Ottawa SAH criteria and recurring symptoms, such as new-onset seizures and high systolic blood pressure, that were identified by EMS. Acute management included administering labetalol, levetiracetam, and ondansetron. Results: Of 2175 stroke patients, 80 screened positive for SAH and were eligible for transfer. Patients had a median age of 66, and 33% had an initial systolic BP over 220 mmHg. The interfacility transfer rate dropped from 12.9 to 3.6% after implementing the protocol. Conclusion: The PCFR protocol's effectiveness suggests its potential for nationwide implementation. Early SAH recognition and prompt transfer to CSCs reduce complications and improve outcomes. Accurate field diagnosis by EMTs can prevent unnecessary transfers and enhance patient care. Future improvements may include portable diagnostic tools and enhanced EMT training to further improve SAH patients' pre-hospital care. [ABSTRACT FROM AUTHOR]

Introduction: Accurately predicting a patient’s prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians’ ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. Methods: Pre-specified secondary analysis of the third intensive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 h and 6 months, (ii) favorable functional outcome (recovery walking and self-care), and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. Results: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5–14) of experience. Of the 6,305 randomized patients who survived 48 h, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99–0.99). Of 5,435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI: 0.92–0.93). Predictions on the favorable functional outcome (PPV 0.54, 95% CI: 0.52–0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI: 0.49–0.52) were poor. Prediction accuracy varied by working years and region of practice. Conclusions: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities. [ABSTRACT FROM AUTHOR]

Background: Predicting long-term survival in intensive care unit patients with intracerebral hemorrhage (ICH) is crucial. This study aimed to develop a platelet-to-white blood cell ratio (PWR) incorporated nomogram for long-term survival prediction. Methods: A retrospective analysis was conducted on 1,728 ICH patients in the MIMIC-IV 2.2 database. The independent prognostic value of PWR for 1- year mortality was assessed. A nomogram was developed using LASSO and Cox regression to predict 1-year survival, incorporating PWR and other factors. The performance of the nomogram was evaluated through calibration curves, area under the curve, Delong test, net reclassification index, integrated discrimination improvement, and decision curve analysis. Results: The nomogram, which included age, weight, Glasgow Coma Scale (GCS) score, mechanical ventilation, glucose, red blood cell (RBC) count, blood urea nitrogen (BUN), and PWR, showed good predictive performance for 1-year survival. The C-index was 0.736 (95% CI = 0.716--0.756) for the training set and 0.766 (95% CI = 0.735--0.797) for the testing set. Higher age and ventilation increased mortality risk, while higher weight, GCS score, RBC count, and PWR decreased risk. The nomogram outperformed conventional scores. Conclusions: A nomogramincorporating PWR as a prognostic factor accurately predicts long-term survival in ICH patients. However, validation in large-scale multicenter studies and further exploration of biomarkers are needed. [ABSTRACT FROM AUTHOR]

Background and purpose: The systemic immune-inflammation index (SII) is a novel immune inflammatory marker which has been proven to have excellent predictive value for many diseases. The aim of this study was to investigate the predictive value of SII at different time points after admission for functional outcome at discharge in patients with intracerebral hemorrhage (ICH). Methods: The clinical data of patients with ICH who were treated at a medical center for neurological diseases in China between October 2012 and April 2022 were analyzed in this retrospective study. The SII was calculated based on neutrophil×platelet/lymphocyte counts and collected within the first 14 days after admission to analyze the dynamic changes. Adverse outcome was defined as a modified Rankin Scale (mRS) score of 4-6 at discharge. The correlation between the SII and the outcome was assessed using univariate and multivariate logistic regression analyses. The ability of SII to predict outcome was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results: A total of 1,569 patients with ICH were included, of whom 790 had adverse outcome (50.35%). The Univariate logistic regression analysis showed that SII at any time point within 14 days after admission was significantly associated with adverse outcome. In the multivariate logistic regression analysis, the SII within 7 days after admission was found to be an independent predictor of adverse functional outcome in ICH patients at discharge. The ROC curve demonstrated that compared to other time points, the SII on day 2 after admission exhibited stronger predictive power for the functional outcome of patients with ICH at discharge (AUC:0.733, 95%CI = 0.679-0.787) (sensitivity 47.09%, specificity 87.02%) (OR 1.074, 95%CI = 1.033-1.126, p = 0.001). Conclusion: SII within 7 days after admission, especially on day 2, is independently associated with adverse functional outcome in ICH patients at discharge. This association could be utilized in clinical practice and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke characterized by high incidence and mortality rates. Currently, there is a significant lack of effective treatments aimed at improving clinical outcomes. Our research team has developed a three-dimensional (3D) biological scaffold that incorporates Bergenin, allowing for the sustained release of the compound. Methods: This 3D biological scaffold was fabricated using a combination of photoinitiator, GEMA, silk fibroin, and decellularized brain matrix (dECM) to encapsulate Bergenin through advanced 3D bioprinting techniques. The kinetics of drug release were evaluated through both in vivo and in vitro studies. A cerebral hemorrhage model was established, and a 3D biological scaffold containing Bergenin was transplanted in situ. Levels of inflammatory response, oxidative stress, and apoptosis were quantified. The neurological function of rats with cerebral hemorrhage was assessed on days 1, 3, and 5 using the turning test, forelimb placement test, Longa score, and Bederson score. Results: The 3D biological scaffold incorporating Bergenin significantly enhances the maintenance of drug concentration in the bloodstream, leading to a marked reduction in inflammatory markers such as IL-6, iNOS, and COX-2 levels in a cerebral hemorrhage model, primarily through the inhibition of the NF-κB pathway. Additionally, the scaffold effectively reduces the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in primary cultured astrocytes, which in turn decreases the production of reactive oxygen species (ROS) and inhibits IL-6 production induced by hemin. Subsequent experiments reveal that the 3D biological scaffold containing Bergenin promotes the activation of the Nrf-2/HO-1 signaling pathway, both in vivo and in vitro, thereby preventing cell death. Moreover, the application of this 3D biological scaffold has been demonstrated to improve drug retention in the bloodstream. Conclusion: This strategy effectively mitigates inflammation, oxidative stress, and cell death in rats with cerebral hemorrhage by inhibiting the NF-κB pathway while concurrently activating the Nrf-2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Background: It is very important to provide the correct nursing care for patients with intracerebral hemorrhage (ICH), but the level of critical care needs in patients with intracerebral hemorrhage is not clear. The purpose of this study is to establish a risk model based on the epidemiological and clinical characteristics of ICH patients, to help identify the critical care needs of ICH patients. Methods: The clinical data of ICH patients from January 2018 to September 2023 were analyzed retrospectively. The full cohort was used to derive the clinical prediction model and the model was internally validated with bootstrapping. Discrimination and calibration were assessed using the area under curve (AUC) and the Hosmer-Lemeshow tests, respectively. Results: 611 patients with ICH were included for model development. 61.21% (374/611) ICH patients had received critical care interventions. The influencing factors included in the model were Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, past blood pressure control, systolic blood pressure on admission and bleeding volume. The model's goodness-of-fit was evaluated, which yielded a high area under the curve (AUC) value of 0.943, indicating a good fit. For the purpose of model validation, a cohort of 260 patients with ICH was utilized. The model demonstrated a Youden's index of 0.750, with a sensitivity of 90.56% and a specificity of 78.22%. Conclusion: GCS, systolic blood pressure, intraventricular hemorrhage, bleeding volume and past blood pressure control are the main factors affecting the critical care needs of patients with ICH. This study has deduced a clinical predictive model with good discrimination and calibration to provide scoring criteria for clinical health care providers to accurately evaluate and identify the critical care needs of ICH patients, to improve the rational integration and allocation of medical resources. [ABSTRACT FROM AUTHOR]

Background: Spontaneous supratentorial intracerebral hemorrhage is the deadliest form of stroke with mortality rates over 50%. Currently, no sufficiently effective treatment to improve both mortality and functional outcome rates exists. However, it seems that minimally invasive surgery, especially endoscopic surgery, might be beneficial in improving survival and functional outcome rates, yet large confirmatory studies thereof are lacking. The aim of this trial is to compare whether early minimally invasive endoscopic surgery leads to improved functional outcome rates compared to the best medical treatment. Methods: This is a prospective, parallel-arm, outcome assessor blinded multicenter trial across Switzerland. Endoscopic surgery will be compared to the best medical treatment in a 1:1 randomization over a total time of 12 months. The primary outcome is defined as improved functional outcome (mRS < 3) after 6 months; secondary outcomes include mortality and morbidity rates as well as patient reported outcomes and the temporal evolution of serum biomarkers for brain damage. Discussion: Currently, large, randomized trials assessing the role and potential effect of early endoscopic surgery in intracerebral hemorrhage are lacking. Potential practical and methodological issues faced in this trial are patient enrollment, adherence to the hematoma evacuation technique used, potential patient cross-over, and the adaptive Bayesian statistical design. Nonetheless, this trial would be among the first to research the effects of early minimally invasive endoscopic surgery for SSICH and can provide class I evidence for future treatment options in intracerebral hemorrhage. Trial registration: ClinicalTrials.gov NCT05681988. Registered on January 3, 2023. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), are frequent complications in patients with intracerebral hemorrhage (ICH). Various prophylactic strategies have been employed to mitigate this risk, such as heparin, intermittent pneumatic compression (IPC), and graduated compression stockings (GCS). The optimal thromboembolic prophylaxis approach remains uncertain due to the lack of randomized controlled trials (RCTs) comparing all interventions. Aims: We conducted a network meta-analysis and meta-analysis to systematically review and synthesize evidence from RCTs and non-randomized studies on the efficacy and safety of thromboembolic prophylaxis strategies in hospitalized ICH patients. Summary of findings: Our study followed a registered protocol (PROSPERO CRD42023489217) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines incorporating the extension for network meta-analyses. Search for eligible studies was performed up to December 2023. We considered the occurrence of DVT, PE, hematoma expansion (HE), and all-cause mortality as outcome measures. A total of 16 studies, including 7 RCTs and 9 non-randomized studies, were included in the analysis. Network meta-analysis revealed that IPC demonstrated the highest efficacy in reducing DVT incidence (odds ratios (OR) 0.30, 95% confidence interval (CI) 0.08–1.16), particularly considering only RCTs (OR 0.33, 95% CI 0.16–0.67). GCS showed the highest safety profile for HE (OR 0.67, 95% CI 0.14–3.13), but without efficacy. Chemoprophylaxis did not reduce the risk of PE events (OR 1.10, 95% CI 0.17–7.19) with a higher occurrence of HE (OR 1.33, 95% CI 0.60–2.96), but the differences were not significant. Conclusion: Our study supports the use of IPC as the primary thromboembolic prophylaxis measure in ICH patients. Further research, including head-to-head RCTs, is needed to strengthen the evidence base and optimize clinical decision-making for thromboembolic prophylaxis in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Background: Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls. Methods: A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2–3, 5–7, and 10–15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t-tests, Chi-square tests, and generalized mixed models. Results: We included 110 patients—43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH—interventional (p = 0.003) and versus the control (p = 0.004), as well as at timepoint 2 for ICH versus SAH—interventional (p = 0.002) and versus SAH—surgical (p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine. Conclusions: In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase. [ABSTRACT FROM AUTHOR]

Introduction: The subarachnoid space in the brain contains crucial blood vessels and cerebrospinal fluid. Aneurysms in these vessels can lead to subarachnoid hemorrhage (SAH), a serious stroke subtype with high morbidity and mortality rates. SAH treatment includes procedures like coiling and clipping, but these are available only at comprehensive stroke centers (CSCs), necessitating urgent diagnosis and transfer to specialized facilities. Methods: This IRB-approved study was conducted by Polk County Fire Rescue (PCFR) in Florida. PCFR, serving an 850,000-person population, implemented a three-step SAH protocol. The protocol uses both Ottawa SAH criteria and recurring symptoms, such as new-onset seizures and high systolic blood pressure, that were identified by EMS. Acute management included administering labetalol, levetiracetam, and ondansetron. Results: Of 2175 stroke patients, 80 screened positive for SAH and were eligible for transfer. Patients had a median age of 66, and 33% had an initial systolic BP over 220 mmHg. The interfacility transfer rate dropped from 12.9 to 3.6% after implementing the protocol. Conclusion: The PCFR protocol's effectiveness suggests its potential for nationwide implementation. Early SAH recognition and prompt transfer to CSCs reduce complications and improve outcomes. Accurate field diagnosis by EMTs can prevent unnecessary transfers and enhance patient care. Future improvements may include portable diagnostic tools and enhanced EMT training to further improve SAH patients' pre-hospital care. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage refers to bleeding caused by non-traumatic rupturing of blood vessels within the brain, which is a serious neurological disorder. Its main pathophysiological characteristics include massive bleeding and neuron death, which impair the neuroimmune system and severely affect the patient’s prognosis. Iron ion homeostasis is crucial for maintaining normal neurological function. However, following intracerebral hemorrhage, disrupted iron metabolism leads to iron accumulation in the brain. Excessive iron participates in neuroinflammatory responses by activating inflammatory signaling pathways and regulating the function of inflammatory cells, while neuroinflammatory cells also participate in regulating the transportation and storage of iron ions. The interaction between the two exacerbates neurol damage. This article reviews the progress of research on the correlation between neuroinflammation and brain iron metabolism after intracerebral hemorrhage, aiming to provide a reference for the clinical treatment of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of penehyclidine hydrochloride (PHC) on the blood-brain barrier (BBB) and the expression of Rho associated coiled-coil containing protein kinase 2 (ROCK2), claudin 5 (CLDN5), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH). Methods A total of 100 SD rats were divided into 20 rats/group as the sham group, the ICH group, the PHC-L group (1 mg/kg PHC), the PHC-M group (2 mg/kg PHC), and the PHC-H group (4 mg/kg PHC). The rat model of ICH was established by autologous blood (50 μL) injection method (except for the sham group). After successful modeling, the rats in the PHC-L, PHC-M, and PHC-H groups were intraperitoneally injected with the corresponding doses of PHC. The sham group and the ICH group were injected with an equal amount of 0.9% sodium chloride solution for 7 consecutive days, once a day. The Longa scoring method was used to score the neurological impairment in rats. A transmission electron microscope was used to observe the ultrastructure of BBB. The Evans blue (EB) method was used to evaluate the permeability of BBB and the water content in rat brain tissue was detected. Immunohistochemical staining and western blot were used to detect the expressions of ROCK2, CLDN5, and AQP-4 in brain tissue. Results Compared with the sham group, the neurological impairment score [0 score vs. (2.45±0.48) score], EB content [(9.75±1.01) μg/g vs. (32.07±3.22) μg/g], brain tissue water content [(77.21±0.33) % vs. (80.96±0.45) %], ROCK2 integrated optical density (IOD) [(1.02±0.14)×10³ vs. (11.05±0.71)×10³ ] and relative expression (0.39±0.03 vs. 1.43±0.24), AQP-4 IOD [(1.67±0.18)×10³ vs. (10.85±0.58)×103 ] and relative expression (0.60±0.07 vs. 1.69±0.21) increased significantly in the ICH group, while the CLDN5 IOD [(10.83±0.64)×10³ vs. (3.02±0.33)×10³ ] and relative expression (1.53±0.20 vs. 0.42±0.06) decreased significantly. Compared with the ICH group, the PHC-L, PHC-M, and PHC-H groups reversed the trend of changes in the aforementioned indicators to varying degrees according to different doses of PHC. Conclusions PHC can ameliorate structural damage to the BBB in ICH rats, potentially through up-regulating the level of CLDN5 and inhibiting the expression of ROCK2 and AQP-4. [ABSTRACT FROM AUTHOR]

Background: Hematoma expansion (HE) after spontaneous intracerebral hemorrhage (ICH) is a severe complication that independently predicts poor prognosis. In this study, we aimed to investigate whether monocyte‐to‐albumin ratio (MAR), a novel marker of systemic inflammation, could predict HE in patients with ICH. Methods: We retrospectively assessed the data of patients with ICH. The clinical, imaging, and laboratory test data including, the MAR on admission, were analyzed. A multivariate logistic regression analysis was carried out to explore the relationship between MAR and hematoma growth. The receiver operating characteristic (ROC) curve was employed to investigate the predictive value of MAR for HE after ICH. Results: A total of 246 patients were included in the present study. Multivariate logistic regression analysis demonstrated that the MAR was associated with HE (odds ratio [OR] = 1.179; 95% confidence interval, 1.093–1.272; p = 0.000). ROC curve analysis showed that MAR could predict HE, with an area under the curve of 0.802 (95% CI: 0.744–0.859, p < 0.001). The optimal predictive cutoff value of MAR for HE was 10.01 (sensitivity: 72.43%, specificity: 77.05%). Conclusions: Our results suggested that a high MAR on admission was associated with an increased risk of HE in ICH patients, and MAR can become an independent predictor of HE in ICH patients. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a serious medical condition associated with high mortality and disability rates. Surgical interventions, including neuroendoscopic surgery (NES) and craniotomy, are employed to manage ICH and improve patient outcomes. This meta-analysis compared the effectiveness of NES versus craniotomy in treating ICH. A systematic literature search was conducted to identify relevant studies comparing NES with craniotomy for ICH. Inclusion criteria encompassed primary or secondary results from randomized controlled trials or observational studies for confirmed supratentorial ICH. Data were extracted, and methodological quality was assessed using appropriate tools. Statistical analysis was performed using meta-analysis software. The analysis included 26studies (N = 3237 patients). NES was associated with significantly lower mortality compared with craniotomy (odds ratio 0.45, 95% confidence interval [CI] 0.33 to 0.60, P < 0.00001). Hematoma evacuation rates were higher with NES (standardized mean difference 1.505, 95% CI 0.835 to 2.160, P < 0.00001). NES also showed better functional outcomes (odds ratio 3.31, 95% CI 1.78 to 6.17, P = 0.0002) and reduced blood loss (standardized mean difference −3.06, 95% CI −3.979 to −2.141, P = 0.000). Additionally, NES was associated with shorter hospital and intensive care unit stays, shorter operative times, and fewer complications such as infection and rebleeding. NES is a promising alternative to craniotomy for treating ICH, offering advantages in terms of reduced mortality, improved functional outcomes, and fewer complications. Future studies should explore advances in neuroendoscopic techniques to optimize patient outcomes further. [ABSTRACT FROM AUTHOR]

Some patients with intracerebral hemorrhage show lesions on diffusion-weighted magnetic resonance imaging, and such lesions have been associated with a greater risk of worse prognosis. Here we meta-analyzed the available evidence for such an association. Studies that reported the presence or absence of lesions on diffusion-weighted imaging (DWI) after intracerebral hemorrhage as well as clinical or radiological outcomes were systematically reviewed and meta-analyzed. Clinical outcome was defined as a score of modified Rankin scale (mRS) at admission to 90 days. Ten studies involving 3575 patients were included in the meta-analysis, and the incidence of DWI lesions ranged from 11.1% to 49.6%. Lesions were associated with a significantly higher risk of poor outcome (mRS scores 3–6) across 6 studies (odds ratio: 2.91; 95% confidence interval: 1.62–5.23; P < 0.001). In subgroup analysis, mRS scores 4–6 were associated with the presence of lesions on DWI (odds ratio: 2.18; 95% confidence interval: 1.31–3.60; P = 0.003). We observed similar results using 3 different definitions of lesions on DWI. Some studies have reported that recurrence of intracerebral hemorrhage was also related with DWI lesions. But there was controversy on the relationship between mortality, ischemic stroke, and hematoma volume and DWI lesions. Lesions on DWI after intracerebral hemorrhage were associated with a higher risk of poor outcome, but large longitudinal studies are needed to verify this association. [ABSTRACT FROM AUTHOR]

Introduction: Intracerebral hemorrhage (ICH) is attributable to cerebral small vessel disease (cSVD), which includes cerebral amyloid angiopathy (CAA) and hypertensive-cSVD (HTN-cSVD). HTN-cSVD includes patients with strictly deep ICH/microbleeds and mixed location ICH/microbleeds, the latter representing a more severe form of HTN-cSVD. We test the hypothesis that more severe forms of HTN-cSVD are related to worse hypertension control in long-term follow-up after ICH. Methods: From consecutive non-traumatic ICH patients admitted to a tertiary care center, we classified the ICH as CAA, strictly deep ICH/microbleeds, and mixed-location ICH/microbleeds. CSVD burden was quantified using a validated MRI-based score (range: 0–6 points). We created a multivariable (linear mixed effects) model adjusting for age, sex, race, year of inclusion, hypertension, and antihypertensive medication usage to investigate the association of average systolic blood pressure (SBP) during follow-up with cSVD etiology/severity. Results: 796 ICH survivors were followed for a median of 48.8 months (IQR 41.5–60.4). CAA-related ICH survivors (n = 373) displayed a lower median SBP (138 mmHg, IQR 133–142 mmHg) compared to those of strictly deep ICH (n = 222, 141 mmHg, IQR 136–143 mmHg, p = 0.04), and mixed location ICH/microbleeds (n = 201, 142 mmHg, IQR 135–144 mmHg, p = 0.02). In the multivariable analysis, mixed location ICH/microbleeds (effect: + 3.8 mmHg, SE: 1.3 mmHg, p = 0.01) and increasing cSVD severity (+ 1.8 mmHg per score point, SE: 0.8 mmHg, p = 0.03) were associated with higher SBP in follow-up. Conclusion: CSVD severity and subtype predicts long-term hypertension control in ICH patients. [ABSTRACT FROM AUTHOR]

Background and purpose: National quality registries for stroke care operate under the assumption that the included patients are correctly diagnosed. We aimed to validate the clinical diagnosis of spontaneous intracerebral hemorrhage (ICH) in Riksstroke (RS) by evaluating radiological data from a large, unselected ICH population. Methods: We conducted a retrospective, multicenter study including all ICH patients registered in RS between 2016 and 2020 residing in Skåne County in Sweden (1.41 million inhabitants). Radiological data from first imaging were evaluated for the presence of spontaneous ICH. Other types of bleeds were registered if a spontaneous ICH was not identified on imaging. The radiological evaluation was independently performed by one radiology fellow and one senior neuroradiologist. Results: Between 2016 and 2020, 1784 ICH cases were registered in RS, of which 1655 (92.8%) had a radiological diagnosis consistent with spontaneous ICH. In the 129 (7.2%) remaining cases, the radiological diagnosis was instead traumatic bleed (n = 80), subarachnoid hemorrhage (n = 15), brain tumor bleed (n = 14), ischemic lesion with hemorrhagic transformation (n = 14), ischemic lesion (n = 3), or no bleed at all (n = 3). There was a higher degree of incorrect coding in the older age groups. Conclusion: At radiological evaluation, 92.8% of ICH diagnoses in RS were consistent with spontaneous ICH, yielding a high rate of agreement that strengthens the validity of the diagnostic accuracy in the register, justifying the use of high coverage quality register data for epidemiological purposes. The most common coding error was traumatic bleeds that were classified as spontaneous ICH. [ABSTRACT FROM AUTHOR]

Background: Men with cerebral amyloid angiopathy (CAA) may have an earlier onset of intracerebral hemorrhage and a more hemorrhagic disease course compared to women. In this cohort study, we investigated sex differences in histopathological markers associated with amyloid-β burden and hemorrhage in cognitively impaired individuals and patients with CAA, using neuropathological data from two autopsy databases. Methods: First, we investigated presence of parenchymal (Thal score) and vascular amyloid-β (CAA severity score) in cognitively impaired individuals from the National Alzheimer's Coordinating Center (NACC) neuropathology database. Next, we examined sex differences in hemorrhagic ex vivo magnetic resonance imaging (MRI) markers and local cortical iron burden and the interaction of sex on factors associated with cortical iron burden (CAA percentage area and vessel remodeling) in patients with pathologically confirmed clinical CAA from the Massachusetts General Hospital (MGH) CAA neuropathology database. Results: In 6120 individuals from the NACC database (45% women, mean age 80 years), the presence of parenchymal amyloid-β (odds ratio (OR) (95% confidence interval (CI)) =0.68 (0.53–0.88)) but not vascular amyloid-β was less in men compared to women. In 19 patients with definite CAA from the MGH CAA database (35% women, mean age 75 years), a lower microbleed count (p < 0.001) but a higher proportion of cortical superficial siderosis and a higher local cortical iron burden was found in men (p < 0.001) compared to women. CAA percentage area was comparable in men and women (p = 0.732). Exploratory analyses demonstrated a possible stronger negative relation between cortical CAA percentage area and cortical iron density in men compared to women (p = 0.03). Conclusion: Previously observed sex differences in hemorrhage onset and progression in CAA patients are likely not due to differences in global CAA severity between men and women. Other factors, such as vascular remodeling, may contribute, but future studies are necessary to replicate our findings in larger data sets and to further investigate the underlying mechanisms behind these complex sex differences. [ABSTRACT FROM AUTHOR]

Background and aim: To investigate the prognostic implication of body mass index (BMI) on clinical outcomes after acute ischemic and hemorrhagic stroke. Methods: The subjects of the study included adult patients with available baseline body weight and height data who had suffered an acute stroke and were registered in the Japan Stroke Data Bank—a hospital-based, multicenter stroke registration database—between January 2006 and December 2020. The outcome measures included unfavorable outcomes defined as a modified Rankin Scale (mRS) score of 5–6 and favorable outcomes (mRS 0–2) at discharge, and in-hospital mortality. Mixed effects logistic regression analysis was conducted to determine the relationship between BMI categories (underweight, normal weight, overweight, class I obesity, class II obesity; <18.5, 18.5–23.0, 23.0–25.0, 25–30, ⩾30 kg/m2) and the outcomes, after adjustment for covariates. Results: A total of 56,230 patients were assigned to one of the following groups: ischemic stroke (IS, n = 43,668), intracerebral hemorrhage (ICH, n = 9741), and subarachnoid hemorrhage (SAH, n = 2821). In the IS group, being underweight was associated with an increased likelihood of unfavorable outcomes (odds ratio, 1.47 (95% confidence interval (CI):1.31−1.65)) and in-hospital mortality (1.55 (1.31−1.83)) compared to outcomes in those with normal weight. Being overweight was associated with an increased likelihood of favorable outcomes (1.09 (1.01−1.18)). Similar associations were observed between underweight and these outcomes in specific IS subtypes (cardioembolic stroke, large artery stroke, and small-vessel occlusion). Patients with a BMI ⩾30.0 kg/m2 was associated with an increased likelihood of unfavorable outcomes (1.44 (1.01−2.17)) and in-hospital mortality (2.42 (1.26−4.65)) in large artery stroke. In patients with ICH, but not those with SAH, being underweight was associated with an increased likelihood of unfavorable outcomes (1.41 (1.01−1.99)). Conclusions: BMI substantially impacts functional outcomes following IS and ICH. Lower BMI consistently affected post-stroke disability and mortality, while higher BMI values similarly affected these outcomes after large artery stroke. [ABSTRACT FROM AUTHOR]

Background and aim: The revised Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) add two radiological markers to the existing criteria: severe visible perivascular spaces in the centrum semiovale and white matter hyperintensities (WMHs) in a multispot pattern. This study aims to determine the sensitivity of the updated criteria in mutation carriers with Dutch-type hereditary CAA (D-CAA) in an early and later disease stage. Methods: In this cross-sectional study, we included presymptomatic and symptomatic D-CAA mutation carriers from our prospective natural history study (AURORA) at the Leiden University Medical Center between 2018 and 2021. 3-Tesla scans were assessed for CAA-related magnetic resonance imaging (MRI) markers. We compared the sensitivity of the Boston criteria v2.0 to the previously used modified Boston criteria v1.5. Results: We included 64 D-CAA mutation carriers (mean age 49 years, 55% women, 55% presymptomatic). At least one white matter (WM) feature was seen in 55/64 mutation carriers (86%: 74% presymptomatic, 100% symptomatic). Fifteen (23%) mutation carriers, all presymptomatic, showed only WM features and no hemorrhagic markers. The sensitivity for probable CAA was similar between the new and the previous criteria: 11/35 (31%) in presymptomatic mutation carriers and 29/29 (100%) in symptomatic mutation carriers. The sensitivity for possible CAA in presymptomatic mutation carriers increased from 0/35 (0%) to 15/35 (43%) with the new criteria. Conclusion: The Boston criteria v2.0 increase the sensitivity for detecting possible CAA in presymptomatic D-CAA mutation carriers and, therefore, improve the detection of the early phase of CAA. [ABSTRACT FROM AUTHOR]

Background: Frequency of imaging markers (FIM) has been identified as an independent predictor of hematoma expansion in patients with intracerebral hemorrhage (ICH), but its impact on clinical outcome of ICH is yet to be determined. The aim of the present study was to investigate this association. Methods: This study was a secondary analysis of our prior research. The data for this study were derived from six retrospective cohorts of ICH from January 2018 to August 2022. All consecutive study participants were examined within 6 h of stroke onset on neuroimaging. FIM was defined as the ratio of the number of imaging markers on noncontrast head tomography (i.e., hypodensities, blend sign, and island sign) to onset-to-neuroimaging time. The primary poor outcome was defined as a modified Rankin Scale score of 3–6 at 3 months. Results: A total of 1253 patients with ICH were included for final analysis. Among those with available follow-up results, 713 (56.90%) exhibited a poor neurologic outcome at 3 months. In a univariate analysis, FIM was associated with poor prognosis (odds ratio 4.36; 95% confidence interval 3.31–5.74; p < 0.001). After adjustment for age, Glasgow Coma Scale score, systolic blood pressure, hematoma volume, and intraventricular hemorrhage, FIM was still an independent predictor of worse prognosis (odds ratio 3.26; 95% confidence interval 2.37–4.48; p < 0.001). Based on receiver operating characteristic curve analysis, a cutoff value of 0.28 for FIM was associated with 0.69 sensitivity, 0.66 specificity, 0.73 positive predictive value, 0.62 negative predictive value, and 0.71 area under the curve for the diagnosis of poor outcome. Conclusions: The metric of FIM is associated with 3-month poor outcome after ICH. The novel indicator that helps identify patients who are likely within the 6-h time window at risk for worse outcome would be a valuable addition to the clinical management of ICH. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage is a major cause of death in humans, with high morbidity, mortality, and disability rates. Secondary brain injury after intracerebral hemorrhage is a consequence of brain edema and neurological dysfunction. Acupuncture is markedly effective against secondary brain injury, and various mechanisms are involved in its action, such as inhibition of inflammatory cascades, inhibition of oxidative stress, attenuation of brain edema, inhibition of nerve cell death, and regulation of neural plasticity. This paper summarizes the mechanism underlying the effects of acupuncture on secondary brain injury after intracerebral hemorrhage in recent years to provide new ideas for subsequent research. [ABSTRACT FROM AUTHOR]

Purpose: The computed tomography angiography (CTA) spot sign is a validated predictor of 30-day mortality in intracerebral hemorrhage (ICH). However, its role in predicting unfavorable functional outcomes remains unclear. This study explores the frequency of the spot sign and its association with functional outcomes, hematoma expansion, and length of hospital stay among survivors of ICH. Materials and methods: This was a retrospective analysis of consecutive patients with primary ICH who received CTA within 24 h of admission to two medical centers between January 2007 and August 2022. Patients who died before discharge and those referred from other hospitals were excluded. Spot signs were assessed by an experienced neuroradiologist. Functional outcomes were determined by modified Rankin Scale (mRS) scores and the Barthel Index (BI). Results: In total, 98 patients were included; 14 (13.64%) had a spot sign. No significant differences were observed in the baseline characteristics between the patients with and without a spot sign. Higher spot sign scores were associated with higher odds of experiencing hematoma expansion (p = 0.013, 95% CI = 1.16–3.55), undergoing surgery (p = 0.012, 95% CI = 0.19–1.55), and having longer hospital stay (p = 0.02, 95% CI = 1.22–13.92). However, higher spot sign scores were not associated with unfavorable functional outcomes (p = 0.918 for BI, and p = 0.782 for mRS). Conclusion: Spot signs are common findings among patients with ICH, and higher spot sign scores were associated with subsequent hematoma expansion and longer hospital stays but not unfavorable functional outcomes. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/β-dystroglycan (β-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10 min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of β-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood–brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated β-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/β-DG pathway after ICH. [ABSTRACT FROM AUTHOR]

Iron overload is associated with brain edema in the context of intracerebral hemorrhage (ICH). Here, we investigated the role of histone deacetylase 1 (HDAC1) in mediating oxidative damage induced by iron overload after ICH. Utilizing ICH mouse models and FeCl2-induced HT-22 cell models, we assessed HDAC1 expression and its impact on iron overload and oxidative damage. We examined the levels of Kruppel like factor 4 (KLF4), RAN binding protein 9 (RANBP9), as well as the acetylation levels of HDAC1 and histones H3 and H4 in the KLF4 promoter, and the KLF4 level in the RANBP9 promoter. Additionally, we investigated the binding relationships between KLF4 and the RANBP9 promoter, HDAC1 and miR-129-5p. Our results demonstrated elevated HDAC1 expression in ICH mice and FeCl2-induced HT-22 cells. HDAC1 silencing improved neurological function in mice, reduced brain edema, and alleviated iron overload and oxidative damage in vitro. HDAC1 downregulated KLF4 expression by reducing acetylation levels in the KLF4 promoter, leading to decreased KLF4 enrichment in the RANBP9 promoter and increased RANBP9 expression. Furthermore, upstream miR-129-5p inhibited HDAC1, and the downregulation of miR-129-5p mitigated the protective effect of HDAC1 silencing. Collectively, our findings highlight the significant role of HDAC1 in exacerbating iron overload-induced oxidative damage following ICH and its regulation by miR-129-5p. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) stands as the most fatal stroke subtype, lacking any specific therapeutic approach yielding benefits for functional recovery. Objectives: We aimed to explore the involvement of long non-coding RNA small nucleolar RNA host gene 3 (lncRNA-SNHG3) in post-ICH neuroinflammation, offering a novel rationale for ICH treatment. Results: Brain tissues of ICH-induced mice exhibited upregulated levels of lncRNA-SNHG3. Inhibition of lncRNA-SNHG3 led to reduced modified neurological severity scores, diminished brain edema, and attenuated inflammatory infiltration, coupled with reduced levels of tumor necrosis factor-α/interleukin-1β. By repressing miR-106b-5p via targeted binding, lncRNA-SNHG3 facilitated the inhibition of transcriptional and protein levels of thioredoxin-interacting protein (TXNIP) through targeted binding to TXNIP mRNA. The counteraction of miR-106b-5p inhibition or the upregulation of TXNIP reversed the ameliorative effect of sh-SNHG3 on neuroinflammation. Conclusion: Competitive binding of lncRNA-SNHG3 to miR-106b-5p resulted in the upregulation of TXNIP, consequently inducing neuroinflammation and exacerbating ICH-induced damage. [ABSTRACT FROM AUTHOR]

Survival of olfactory mucosal mesenchymal stem cells (OM-MSCs) remains the low level in the cerebral microenvironment during intracerebral hemorrhage (ICH). This article aims to reveal the differential expression profile of ICH-stimulated OM-MSCs based on whole transcriptome sequence analysis. OM-MSCs were isolated from 6-week C57BL/6 mice. Morphology and surface markers of OM-MSCs were investigated by light microscope and flow cytometry, respectively. OM-MSCs were incubated with 20 U/mL thrombin for 24 h to mimic ICH-induced injury in vitro. Total RNA was extracted for whole transcriptome sequencing and qPCR. OM-MSCs were characterized by negative for CD45 and CD34, and positive for CD44, CD90 and CD29. Thrombin led to decrease in cell viability and increase in senescence and apoptosis in OM-MSCs. In total, 736 lncRNAs (upregulated: 393; downregulated: 343), 21 miRNAs (upregulated: 7; downregulated: 14) and 807 mRNAs (upregulated: 422; downregulated: 385) were identified. GO and KEGG pathways were enriched in protein heterodimerization activity, trans-synaptic signaling, membrane pathway, alcohol metabolic process, organic hydroxy compound biosynthesis process, secondary alcohol metabolic process, alcoholism, neutrophil extracellular trap formation, systemic lupus erythematosus, metabolic process, steroid biosynthesis and drug metabolism-cytochrome P450. 200 lncRNA-miRNA-mRNA were predicted in thrombin-induced OM-MSCs. Based on qPCR, we validated COMMD1B, MOAP1, lncRNA CAPN15, lncRNA ALDH1L2, miR-3473b and miR-1964-3p were upregulated in thrombin-stimulated OM-MSCs, and GM20431, lncRNA GAPDH and miR-122b-3p were downregulated. Our findings provide novel understanding for thrombin-induced injury in OM-MSCs. Differently-expressed RNAs can be the targets of improving therapeutic application of OM-MSCs. [ABSTRACT FROM AUTHOR]

Deep intracerebral hemorrhage (ICH) exerts a direct force on corticospinal tracts (CST) causing shape deformation. Using serial MRI, Generalized Procrustes Analysis (GPA), and Principal Components Analysis (PCA), we temporally evaluated the change in CST shape. Thirty-five deep ICH patients with ipsilesional-CST deformation were serially imaged on a 3T-MRI with a median imaging time of day-2 and 84 of onset. Anatomical and diffusion tensor images (DTI) were acquired. Using DTI color-coded maps, 15 landmarks were drawn on each CST and the centroids were computed in 3 dimensions. The contralesional-CST landmarks were used as a reference. The GPA outlined the shape coordinates and we superimposed the ipsilesional-CST shape at the two-time points. A multivariate PCA was applied to identify eigenvectors associated with the highest percentile of change. The first three principal components representing CST deformation along the left-right (PC1), anterior-posterior (PC2), and superior-inferior (PC3) respectively were responsible for 57.9% of shape variance. The PC1 (36.1%, p < 0.0001) and PC3 (9.58%, p < 0.01) showed a significant deformation between the two-time points. Compared to the contralesional-CST, the ipsilesional PC scores were significantly (p < 0.0001) different only at the first-timepoint. A significant positive association between the ipsilesional-CST deformation and hematoma volume was observed. We present a novel method to quantify CST deformation caused by ICH. Deformation most often occurs in left-right axis (PC1) and superior-inferior (PC3) directions. As compared to the reference, the significant temporal difference at the first time point suggests CST restoration over time. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a critical neurological disease caused by the rupture of blood vessels within the brain parenchyma, with high mortality and morbidity rates. Currently, much research has focused on the injury mechanisms and intervention strategies following ICH, yet clinically effective treatments that significantly improve patient outcomes remain scarce. The mass effect refers to the mechanical compression of brain tissue by the hematoma during ICH, and its crucial role in neural function damage has been widely recognized in clinical practice. Therefore, exploring the mechanisms and pathways of the mass effect mediating primary and secondary injuries after ICH holds significant practical importance for the development of clinical intervention strategies. This article reviews the injury mechanisms and pathways of the mass effect during the onset and progression of ICH, aiming to provide references and theoretical bases for intervention research following ICH. [ABSTRACT FROM AUTHOR]

Background: Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates neuroinflammation. This study aimed to determine the prognostic role of serum IRAK3 in acute intracerebral hemorrhage (ICH). Methods: In this prospective observational cohort study, 152 patients with supratentorial ICH, along with 63 healthy controls, were recruited. Serum IRAK3 levels were measured at the time of enrollment for controls, at admission for all patients, and on poststroke days 1, 3, 5, 7, 10, and 15 in a subset of 63 patients. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poststroke 6-month modified Rankin Scale (mRS) scores were registered, with scores of 3--6 representing a poor prognosis. Multivariate models were established to investigate severity correlation and prognosis association. Results: Serum IRAK3 levels were significantly elevated at the admission of patients, peaked at day 1, plateaued at day 3, gradually declined until day 15, and were substantially higher over the first 15 days poststroke than in controls. Admission serumIRAK3 levels were independently associated with NIHSS scores, hematoma volume, and 6-month mRS scores in a multivariate linear regression model. They were linearly correlated with the risk of poor prognosis in a restricted cubic spline analysis and were independently predictive of poor prognosis in a binary logistic regression model. Additionally, they demonstrated strong prognostic ability in the receiver operating characteristic curve analysis. Using subgroup analysis, no interactions were found between admission serum IRAK3 levels and some routine variables, such as age, gender, hypertension, and diabetes mellitus. Moreover, the model combining admission serum IRAK3, NIHSS scores, and hematoma volume demonstrated stability and clinical value in calibration and decision curve analyses. Conclusion: A significant increase in serum IRAK3 levels during the early phase after ICH, strongly correlated with disease severity, is independently associated with a poor 6-month prognosis, establishing serum IRAK3 as a valuable prognostic biomarker for ICH. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ferroptosis of neurons is a significant cause of brain injury following intracerebral hemorrhage (ICH). As an iron-containing compound in hemoglobin, heme contributes to nerve injury post-ICH. Melatonin has been shown to mitigate the effects of ICH, yet its specific functions remain largely elusive. In this study, we aimed to explore the roles and mechanisms of melatonin in heme-induced ferroptosis subsequent to ICH. MATERIALS AND METHODS: C57BL/6 mice were intracranially injected with heme and then treated with melatonin. Behavior tests [modified neurological severity score (mNSS), forelimb placing, and corner turn tests], H&E staining, Nissl staining, and Prussian blue staining were used to evaluate mouse brain tissue injury. In vitro, HT-22 cells were stimulated with heme and cell viability was determined by crystal violet staining. The iron contents were determined in heme-treated brains and cells, and the levels of 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA) were assessed by ELISA. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Immunoblotting was used to analyze the protein expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Finally, small interfering RNA (siRNA) was used to knock down Nrf2 in HT-22 cells. RESULTS: Melatonin treatment alleviated heme-induced injuries to neural function, as indicated by improved behavior in the mice. Moreover, melatonin decreased cell death and iron concentrations, increased MDA and 4-HNE levels, and reversed the decreases in GPX4, SLC7A11, Nrf2, and HO-1 induced by heme in vitro and in vivo. These results indicated that melatonin could improve the ferroptosis induced by heme. In addition, we found that Nrf2 knockdown attenuated the therapeutic effect of melatonin on neuronal ferroptosis induced by heme. CONCLUSIONS: In general, melatonin alleviates heme-induced ferroptosis by activating the Nrf2/HO-1 pathway, which implies that melatonin is a promising treatment for ferroptosis in ICH. [ABSTRACT FROM AUTHOR]

Background: Associations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH). Aim: The associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively. Methods: We have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode. Results: One hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649). Conclusion: We observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c. [ABSTRACT FROM AUTHOR]

• Single-cell sequencing has identified three ICH-related microglial subtypes. • Certain ICH-related microglia subtypes share features with those in other diseases. • Phagocytic and lipid-handling microglia might develop from early proliferating ones. Microglia are important innate immune cells in the brain, and a rich diversity of subtypes has recently been discovered that expand beyond the traditional classification of traditional M1 (pro-inflammatory) and M2 (anti-inflammatory) classifications. Intracerebral hemorrhage (ICH) is a devastating form of stroke, and the understanding of its later-stage pathological mechanisms remains incomplete. In this study, through the analysis of single-cell transcripts from mice brains 14 days post-ICH, three disease-associated expression patterns of microglia were identified. These include a lipid metabolism and phagocytosis phenotype reminiscent of Disease-Associated Microglia (DAM) initially discovered in Alzheimer's disease models, a phenotype associated with angiogenesis, and a relatively independent phenotype similar to the pro-inflammatory M1 state. These findings were further validated through immunofluorescence in both mouse and human specimens. In addition, analysis of single-cell transcripts from mice brains 3 days post-ICH suggested that microglia involved in lipid metabolism and phagocytosis likely emerge from early proliferating populations. Given the distinct origins and phenotypic characteristics of pro-inflammatory and reparative microglia, interventions targeting these cells hold the potential to modulate the delicate balance between injury and repair during the pathophysiological process of ICH, highlighting a pivotal direction for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers. Methods: We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes. Results: In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH. Conclusions: This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) results from the rupture of blood vessels causing bleeding within the brain and is one of the major causes of death and long-term disability globally, particularly in low- and middle-income countries. Despite having a lower incidence than ischemic stroke, ICH imposes a greater social and economic burden. To our knowledge, since the release of the 2021 Global Burden of Disease (GBD) report, there has been no comprehensive update on the epidemiology and trends of ICH. This study aims to analyze the impact of gender, age, and the Sociodemographic Index (SDI) on the burden of ICH at global, regional, and national levels. Methods: Data on the incidence, deaths, and disability-adjusted life years (DALYs) of ICH and its related risk factors from 1990 to 2021 were extracted from the GBD 2021 project, encompassing 203 countries and regions. Furthermore, temporal trends of the global intracerebral hemorrhage burden were assessed through Joinpoint analysis. Results: In 2021, there were 3.444 million new cases of ICH worldwide, with an age-standardized prevalence rate of 40.8 per 100,000 people, representing a 31.4% decrease compared to 1990. In 2021, ICH caused 3.308 million deaths, with an age-standardized mortality rate of 39.1 per 100,000 people, a reduction of 36.6% since 1990. Globally, ICH accounted for 79.457 million DALYs, with an age-standardized DALY rate of 92.4 per 100,000 people, representing a 39.1% decrease since 1990. Regionally, Central Asia, Oceania, and Southeast Asia had the highest age-standardized prevalence rates of ICH, whereas Australasia, high-income North America, and Western Europe had the lowest rates. Nationally, the Solomon Islands, Mongolia, and Kiribati had the highest age-standardized prevalence rates, whereas Switzerland, New Zealand, and Australia had the lowest. Hypertension, smoking, and environmental pollution were identified as the primary risk factors for ICH. This study also validated the significant association between SDI and the burden of ICH, with the age-standardized DALY rate of ICH decreasing significantly as SDI increased. Conclusion: Despite the decreasing burden of intracerebral hemorrhage, it remains a significant public health issue in countries with a lower SDI. Prevention strategies should prioritize hypertension management, air quality improvement, and smoking control to further mitigate the impact of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of honokiol on neurological injury and cognitive function in mice with intracerebral hemorrhage (ICH) and its mechanism. Methods C57BL/6J mice were randomly grouped into the sham operation group, the model group, the low, medium, and high dose honokiol groups, and the honokiol+inhibitor group. Except for the sham operation group, ICH models were established by injecting autologous blood into the right basal ganglia in other groups. At 15 min before ICH and 1 h after ICH, the low, medium, and high dose honokiol groups were intraperitoneally injected with 10 mg/kg, 20 mg/kg, and 40 mg/kg honokiol, respectively. The honokiol+inhibitor group was intraperitoneally injected with 40 mg/kg honokiol and 5 μg/kg brain derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB)- cyclic adenosine monophosphate response element binding protein (CREB) signaling pathway inhibitor K252a. The sham operation group and the model group were intraperitoneally injected with equal amounts of dimethyl sulfoxide and physiological saline. The modified neurological severity score (mNSS) was applied to assess the neurological function of mice. The Morris water maze experiment was applied to evaluate the spatial learning and memory abilities of mice by calculating the escape latency, the number of times of crossing the original platform, and the percentage of residence time in the target quadrant. Hematoxylin-eosin (HE) staining was applied to observe the pathological changes in hippocampal neurons. Terminal-deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling (TUNEL) staining was applied to detect the apoptotic rate of hippocampal neurons. Enzyme-linked immunosorbent assay (ELISA) was applied to detect serum levels of BDNF and TrkB. Western blot was applied to detect the expression of BDNF, TrkB, CREB, and phosphorylated CREB (p-CREB) proteins in the hippocampus. Results Compared with the sham operation group, the mNSS and apoptotic rate of hippocampal neurons in the model group increased, the escape latency prolonged, the number of times of crossing the original platform decreased, the percentage of residence time in the target quadrant decreased, and the levels of BDNF, TrkB in serum and BDNF, TrkB, p-CREB/CREB in the hippocampus decreased (all P<0.001). The structure of hippocampal neurons was blurred, the arrangement was disordered, the number was reduced, the volume was smaller, and the nucleus was shrunk. Compared with the model group, the mNSS (all P<0.01) and apoptotic rate of hippocampal neurons (all P<0.001) in mice in the low, medium, and high dose honokiol groups decreased successively, the escape latency (all P<0.001) shortened successively, the number of times of crossing the original platform (P=0.007, P<0.001, P<0.001) increased successively, the percentage of residence time in the target quadrant (P=0.004, P<0.001, P<0.001) increased successively, and the levels of BDNF (all P<0.001), TrkB (P=0.001, P<0.001, P<0.001) in serum and BDNF (P=0.008, P<0.001, P<0.001), TrkB (P=0.001, P<0.001, P<0.001), p-CREB/CREB (all P<0.001) in the hippocampus increased successively, the damage of hippocampal neurons was improved. Compared with the high dose honokiol group, the mNSS and apoptotic rate of hippocampal neurons in the honokiol+inhibitor group were increased, the escape latency was prolonged, and the number of times of crossing the original platform was decreased, the percentage of residence time in the target quadrant was decreased, and the levels of BDNF, TrkB in serum and BDNF, TrkB, and p-CREB/CREB in the hippocampus were decreased (all P<0.001), and the damage of hippocampal neurons was aggravated. Conclusions Honokiol may alleviate hippocampal neuronal apoptosis and damage, and improve cognitive dysfunction in ICH mice by activating the BDNF-TrkB-CREB signaling pathway [ABSTRACT FROM AUTHOR]

Background: Differential diagnosis between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is a great challenge. Recently, the discovery of cerebral lymphatic drainage toward the nostrils suggested nasal exudate (NE) as a new source for measuring biomarkers from neural damage. Objectives: In this study, we sought to confirm whether glial fibrillary acidic protein (GFAP) levels in NE could identify ICH. Methods: GFAP in nasal exudate (nGFAP) was studied in 5 IS and 5 ICH patients. All patients underwent neurological examination, brain computed tomography, laboratory tests, and measurement of nGFAP and serum GFAP. Results: We found higher concentrations in ICH patients (p = 0.02). The area under the ROC curve for IS/ICH discrimination was 0.840, with a cut-off point of 0.06 pg/mg for 100% sensitivity and 80% specificity. Conclusions: These findings suggest that nGFAP could be a useful biomarker for differential diagnosis between IS and ICH and opens a potential field of study for other biomarkers in NE in neurological disorders. [ABSTRACT FROM AUTHOR]

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13–44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%–9.08% and the intra-assay CV of 4.75%–7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke. [ABSTRACT FROM AUTHOR]

Although most laminin isoforms are neuroprotective in stroke, mural cell-derived laminin-α5 plays a detrimental role in an ischemia-reperfusion model. To determine whether this deleterious effect is an intrinsic feature of mural cell-derived laminin-α5 or unique to ischemic stroke, we performed loss-of-function studies using middle-aged mice with laminin-α5 deficiency in mural cells (α5-PKO) in an intracerebral hemorrhage (ICH) model. Control and α5-PKO mice exhibited comparable changes in all parameters examined, including hematoma size, neuronal death, neurological function, blood-brain barrier integrity, and reactive gliosis. These findings highlight a minimal role of mural cell-derived laminin-α5 in ICH. Together with the detrimental role of mural cell-derived laminin-α5 in ischemic stroke, these negative results in ICH model suggest that mural cell-derived laminin-α5 may exert distinct functions in different diseases. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a severe hemorrhagic stroke and induces severe secondary neurological injury. However, its pathogenesis remains to be explored. The present work investigates the role of glutathione S‐transferase omega 2 (GSTO2) in ICH and the underlying mechanism. Human neuroblastoma cells (SK‐N‐SH) were stimulated using hemin to mimic ICH‐like injury. Protein expression levels of GSTO2 and glutathione peroxidase 4 (GPX4) were detected by western blot analysis assay. Cell viability was assessed by cell counting kit‐8 assay. Cell proliferation was investigated by 5‐ethynyl‐2′‐deoxyuridine assay. Cell apoptosis was analyzed by flow cytometry. Interleukin‐6 and tumor necrosis factor‐α levels were quantified by enzyme‐linked immunosorbent assays. Fe2+ colorimetric assay kit was used to detect Fe2+ level. A cellular reactive oxygen species (ROS) assay kit was used to detect ROS levels. Malondialdehyde (MDA) level was assessed using the MDA content assay kit. GSH level was quantified using the GSH assay kit. Co‐immunoprecipitation assay was performed to identify the association between GSTO2 and GPX4. Hemin stimulation suppressed SK‐N‐SH cell proliferation and promoted cell apoptosis, cell inflammation, ferroptosis, and oxidative stress. GSTO2 expression was downregulated in hemin‐treated SK‐N‐SH cells in comparison with the control group. In addition, ectopic GSTO2 expression counteracted hemin‐induced inhibitory effect on cell proliferation and promoting effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress. Moreover, GSTO2 was associated with GPX4 in SK‐N‐SH cells. GPX4 silencing attenuated GSTO2 overexpression‐induced effects on hemin‐stimulated SK‐N‐SH cell injury. GSTO2 ameliorated SK‐N‐SH cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in ICH, providing a therapeutic strategy for ICH. [ABSTRACT FROM AUTHOR]