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Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH‐induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood‐induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single‐cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP‐activated exchange protein‐1 (EPAC‐1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC‐1) to inhibit its interaction with voltage‐dependent anion‐selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron‐specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC‐1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC‐1 with celastrol can be a promising therapeutic approach for treating ICH‐induced SBI. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is characterized by hematoma development within the brain's parenchyma, contributing significantly to the burden of stroke. While non-contrast head computed tomography (CT) remains the gold standard for initial diagnosis, this review underscores the pivotal role of magnetic resonance imaging (MRI) in ICH management. Beyond diagnosis, MRI offers invaluable insights into ICH etiology, prognosis, and treatment. Utilizing echo-planar gradient-echo or susceptibility-weighted sequences, MRI demonstrates exceptional sensitivity and specificity in identifying ICH, aiding in differentiation of primary and secondary causes. Moreover, MRI facilitates assessment of hemorrhage age, recognition of secondary lesions, and evaluation of perihematomal edema progression, thus guiding tailored therapeutic strategies. This comprehensive review discusses the multifaceted utility of MRI in ICH management, highlighting its indispensable role in enhancing diagnostic accuracy as well as aiding in prognostication. As MRI continues to evolve as a cornerstone of ICH assessment, future research should explore its nuanced applications in personalized care paradigms. [ABSTRACT FROM AUTHOR]

Background: Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events. Objectives: We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS versus dICH in a cross-sectional study. Methods: We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH. Results: A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% versus 74.8%, p = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25–0.48), 0.32 (0.22–0.44), 0.31 (0.22–0.44), and 0.38 (0.18–0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68–3.28), 2.53 (1.31–4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11–0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35–5.27), 4.95 (2.71–9.42)]. WMH burden and spatial distribution did not differ between groups. Conclusion: The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. Objective: To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Methods: Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Results: Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, p = 0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5 ng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829–12.189, p = 0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, p = 0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Conclusions: Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence. [ABSTRACT FROM AUTHOR]

The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Hematoma expansion is a critical factor associated with increased mortality and adverse outcomes in patients with intracerebral hemorrhage (ICH). Identifying and preventing hematoma expansion early on is crucial for effective therapeutic intervention. This study aimed to investigate the potential association between the Red cell distribution width to lymphocyte ratio (RDWLR) and hematoma expansion in ICH patients. Methods: We conducted a retrospective analysis of clinical data from 303 ICH patients treated at our department between May 2018 and May 2023. Demographic, clinical, radiological, and laboratory data, including RDWLR upon admission, were assessed. Binary logistic regression analysis was employed to determine independent associations between various variables and hematoma expansion. Results: The study included 303 ICH patients, comprising 167 (55.1%) males and 136 (44.9%) females, with a mean age of 65.25 ± 7.32 years at admission. Hematoma expansion occurred in 73 (24.1%) cases. Multivariate analysis revealed correlations between hematoma volume at baseline (OR, 2.73; 95% CI: 1.45 -4,78; P < 0.001), admission systolic blood pressure (OR, 2.98 ; 95% CI: 1.54–4.98; P < 0.001), Glasgow Coma Scale (GCS) (OR, 1.58; 95% CI: 1.25–2.46; P = 0.017), and RDWLR (OR, 1.58; 95% CI: 1.13–2.85; P = 0.022) and hematoma expansion in these patients. Conclusions: Our findings suggest that RDWLR could serve as a new inflammatory biomarker for hematoma expansion in ICH patients. This cost-effective and readily available biomarker has the potential for early prediction of hematoma expansion in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-bactivated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. Methods: Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays. Results: Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. Discussion: Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH. [ABSTRACT FROM AUTHOR]

Background: The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. Methods: In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Results: Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Conclusion: Radscore_PHE, based on Shape_VoxelVolume and Shape_ MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury. Activating transcription factor 4 (ATF4) is a member of the transcription activator family, which plays an important role in secondary brain injury after intracerebral hemorrhage. However, the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE: To explore the effect of ATF4 silencing (ATF4 small interfering RNA, ATF4 siRNA) on neuronal necroptosis after intracerebral hemorrhage. METHODS: The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured, and hemin was used to mimic an in vitro model of intracerebral hemorrhage. A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L, and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin. The cells were divided into four groups: the blank control group without any intervention; the control group was treated with hemin (50 μmol/L), and the other two groups were treated with negative control small interfering RNA (NC siRNA) and ATF4 small interfering RNA (ATF4 siRNA) 48 hours before administration of hemin. After the cells were treated with hemin (50 μmol/L) for 24 hours, PI/Hoechst staining was used to detect neuronal necroptosis. Western blot assay was used to detect the protein expression of ATF4, receptor-interacting protein 3 (RIP3), and mixed lineage kinase domain-like protein (MLKL), and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION: (1) 50 μmol/L of hemin could induce neuronal necroptosis to a greater extent. (2) The number of PI+ /Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group (P < 0.000 1). The number of PI+ /Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group (P < 0.000 1). (3) Compared with the control group, the ATF4 siRNA group not only inhibited the expression of ATF4 protein (P < 0.001), but also inhibited the expression of RIP3 and MLKL protein (P < 0.001). (4) Through double immunofluorescent staining, compared with the control group, the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group (P < 0.000 1). (5) The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage, and play a vital role in alleviating secondary brain injury. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance diffusion-weighted imaging (DWI) is the most sensitive modality for ischemic stroke diagnosis. However, DWI may fail to detect ischemic lesions in a proportion of patients. Methods: Following PRISMA statement, a systematic search of Medline, Embase, and Web of Science was conducted until January 3, 2024. The inclusion was confined to English literature with sufficient reporting. Proportions of DWInegative ischemic stroke were pooled. For binary variables, odds ratios (ORs) were computed using the random-effects model. Results: Fourteen studies constituting 16,268 patients with a clinical diagnosis of ischemic stroke and available DWI findings were included. Intravenous thrombolysis (IVT) was administered to 19.6% of the DWI-negative group and 15.3% of the DWI-positive group. DWI-negative ischemic stroke was reported in 16% (95% CI: 10-24%; after sensitivity analysis: 11% [95% CI: 8-15%]) of stroke patients. Among minor stroke patients (National Institutes of Health Stroke scale [NIHSS] of 5 or less), 24% (95% CI 12-42%) had negative DWI findings. Predictors of DWI-negative scans included posterior circulation stroke, history of ischemic heart disease, prior stroke, or prior transient ischemic attack. Cardioembolic stroke (OR, 0.62, 95% CI: 0.41-0.93) and history of atrial fibrillation increased the likelihood of positive DWI findings (OR, 0.56, 95% CI: 0.45-0.71). Patients with DWI-negative ischemic stroke had higher odds of good functional outcomes (modified Rankin scale [mRS] of 0-1) (OR, 2.26; 95% CI: 1.03-4.92), lower odds of stroke recurrence (OR, 0.68; 95% CI: 0.48-0.96), and lower odds of severe disability or mortality (mRS of 3-6) (OR, 0.44; 95% CI: 0.34-0.57) compared to patients with positive DWI. Rates of symptomatic intracerebral hemorrhage after IVT were comparable between groups. Conclusion: DWI-negative findings were present in a significant proportion of ischemic stroke patients and may be utilized as a marker for favorable prognosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Txnrd2 may be involved in brain injury caused by intracerebral hemorrhage (ICH) • Txnrd2 increased in neurons, astrocytes cells post-ICH. • Txnrd2 knockdown increased the levels of oxidative stress and ER-stress in the brain post-ICH. • Se may partly alleviate the early brain injury after ICH caused by oxidative stress and ER stress via Txnrd2. • Txnrd2 may represent a therapeutic target for ICH. Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. Primarily, expression and localization of Txnrd2, Trx2 and Prx3 were determined in collagenase IV-induced ICH model. Txnrd2 was then knocked down using siRNA interference in rats which were found to develop more severe encephaledema and neurological deficits. Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target. [ABSTRACT FROM AUTHOR]

• M1/M2 macrophages exhibit varying ratios at different times after cerebral hemorrhage. • Nrdp1 overexpression regulates the polarization of M2 macrophages. • Nrdp1 promotes neurological recovery in the early stages after cerebral hemorrhage. Neuregulin receptor degradation protein 1 (Nrdp1) is a ring finger E3 ubiquitin ligase involved in some inflammation through ubiquitination, including macrophage polarization following cerebral hemorrhage. However, there is limited understanding regarding the mechanisms through which Nrdp1 modulates macrophage polarization and the potential impact of this modulation on neurological function. Using stereotactic injection and adenoviral transfection techniques, the corresponding animal models were constructed through injecting adenovirus, saline, or blood into the mouse striatum at different periods of time in this research. The alteration in the ratio of various M1/M2 phenotype-associated markers (e.g., CD86, CD206, IL-6, IL-10, etc.) was evaluated through immunohistochemistry, immunofluorescence, western blotting, and elisa assays. Additionally, neurological function scores and behavioral tests were utilized to evaluate changes in neurological function in mice after cerebral hemorrhage. Our results show that overexpression of Nrdp1 promotes the expression of a variety of M2 macrophage-associated markers and enhance transcriptional activity of arginase-1 (Arg1) protein through ubiquitination for early regulation M2 macrophage polarization. Additionally, Nrdp1 promotes hematoma absorption, increases IL-10 expression, inhibits inducible nitric oxide synthase (iNOS), IL-6, and TNF-α production, alleviates neurological impairment and brain edema, and accelerates functional recovery. These findings suggest that modulating macrophage polarization through Nrdp1 could be a therapeutic strategy for neurofunctional impairment in cerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. Methods: ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Results: Sixty patients were randomized with a mean  ±  SD age of 57.5  ±  10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5–0.9) mL vs. SC group 0.91 (0.5–1.2) mL, p  =  0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3–0.8) cm vs. SC group 0.51 (0.3–0.8) cm, p  =  0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6–1.2) cm vs. SC group 1 (0.9–1.2) cm, p  =  0.75). Conclusions: Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention. [ABSTRACT FROM AUTHOR]

Background: to examine factors associated with cardiac evaluation and associations between cardiac test abnormalities and clinical outcomes in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous subarachnoid hemorrhage (SAH), spontaneous intracerebral hemorrhage (sICH), and traumatic brain injury (TBI) requiring neurocritical care. Methods: In a cohort of patients ≥18 years, we examined the utilization of electrocardiography (ECG), beta-natriuretic peptide (BNP), cardiac troponin (cTnI), and transthoracic echocardiography (TTE). We investigated the association between cTnI, BNP, sex-adjusted prolonged QTc interval, low ejection fraction (EF < 40%), all-cause mortality, death by neurologic criteria (DNC), transition to comfort measures only (CMO), and hospital discharge to home using univariable and multivariable analysis (adjusted for age, sex, race/ethnicity, insurance carrier, pre-admission cardiac disorder, ABI type, admission Glasgow Coma Scale Score, mechanical ventilation, and intracranial pressure [ICP] monitoring). Results: The final sample comprised 11,822 patients: AIS (46.7%), sICH (18.5%), SAH (14.8%), and TBI (20.0%). A total of 63% (n = 7472) received cardiac workup, which increased over nine years (p < 0.001). A cardiac investigation was associated with increased age, male sex (aOR 1.16 [1.07, 1.27]), non-white ethnicity (aOR), non-commercial insurance (aOR 1.21 [1.09, 1.33]), pre-admission cardiac disorder (aOR 1.21 [1.09, 1.34]), mechanical ventilation (aOR1.78 [1.57, 2.02]) and ICP monitoring (aOR1.68 [1.49, 1.89]). Compared to AIS, sICH (aOR 0.25 [0.22, 0.29]), SAH (aOR 0.36 [0.30, 0.43]), and TBI (aOR 0.19 [0.17, 0.24]) patients were less likely to receive cardiac investigation. Patients with troponin 25th–50th quartile (aOR 1.65 [1.10–2.47]), troponin 50th–75th quartile (aOR 1.79 [1.22–2.63]), troponin >75th quartile (aOR 2.18 [1.49–3.17]), BNP 50th-75th quartile (aOR 2.86 [1.28–6.40]), BNP >75th quartile (aOR 4.54 [2.09–9.85]), prolonged QTc (aOR 3.41 [2.28; 5.30]), and EF < 40% (aOR 2.47 [1.07; 5.14]) were more likely to be DNC. Patients with troponin 50th–75th quartile (aOR 1.77 [1.14–2.73]), troponin >75th quartile (aOR 1.81 [1.18–2.78]), and prolonged QTc (aOR 1.71 [1.39; 2.12]) were more likely to be associated with a transition to CMO. Patients with prolonged QTc (aOR 0.66 [0.58; 0.76]) were less likely to be discharged home. Conclusions: This large, single-center study demonstrates low rates of cardiac evaluations in TBI, SAH, and sICH compared to AIS. However, there are strong associations between electrocardiography, biomarkers of cardiac injury and heart failure, and echocardiography findings on clinical outcomes in patients with ABI. Findings need validation in a multicenter cohort. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0–37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage (ICH) poses a public health issue due to its elevated mortality rates. The International Normalized Ratio-platelet index (INR-Plt index) has recently been recognized as a predictive factor for liver disease progression. The potential of applying the INR-Plt index in forecasting ICH prognosis presents an intriguing subject. This study endeavors to examine the correlation between the INR-Plt index and hospital outcomes in patients with spontaneous supratentorial ICH. A retrospective examination of 283 adult ICH patients was undertaken. The INR-Plt index was computed using the formula: [INR/platelet counts (1000/μL)] × 100. The clinical outcomes evaluated consisted of mortality rates and the Modified Rankin Scale (mRS) at discharge. An unfavorable outcome was defined as an mRS score from 4 to 6. The study found a significant correlation between the INR-Plt index and hospital mortality (odds ratio: 4.31, 95% CI: 1.07–17.31, P = 0.04). There was a 43% rise in mortality risk for every 0.1 unit increase in the INR-Plt index. Kaplan–Meier survival curves illustrated a considerably lower survival rate at discharge for patients with an INR-Plt index >0.8 (log-rank test: P = 0.047). Regarding unfavorable outcomes, the INR-Plt index was not a significant factor according to logistic regression analyses. The INR-Plt index is a predictor of hospital mortality in patients with spontaneous supratentorial ICH. A higher INR-Plt index value is associated with an increased risk of mortality, underlining the potential usefulness of this composite index in guiding clinical decision-making and enabling risk stratification. [ABSTRACT FROM AUTHOR]

The significance of noncontrast computer tomography (CT) image markers in predicting hematoma expansion (HE) following intracerebral hemorrhage (ICH) within different time intervals in the initial 24 hours after onset may be uncertain. Hence, our objective was to examine the predictive value of clinical factors and CT image markers for HE within the initial 24 hours using machine learning algorithms. Four machine learning algorithms, including extreme gradient boosting (XGBoost), support vector machine, random forest, and logistic regression, were employed to assess the predictive efficacy of HE within every 6-hour interval during the first 24 hours post-ICH. The area under the receiver operating characteristic curves was utilized to appraise predictive performance across various time periods within the initial 24 hours. A total of 604 patients were included, with 326 being male, and 112 experiencing hematoma expansion (HE). The findings from machine learning algorithms revealed that computed tomography (CT) image markers, baseline hematoma volume, and other factors could accurately predict HE. Among these algorithms, XGBoost demonstrated the most robust predictive model results. XGBoost's accuracy at different time intervals was 0.89, 0.82, 0.87, and 0.94, accompanied by F1-scores of 0.89, 0.80, 0.87, and 0.93, respectively. The corresponding area under the curve was 0.96, affirming the precision of the predictive capability. Computed tomography (CT) imaging markers and clinical factors could effectively predict HE within the initial 24 hours across various time periods by machine learning algorithms. In the expansive landscape of big data and multimodal cerebral hemorrhage, machine learning held significant potential within the realm of neuroscience. [ABSTRACT FROM AUTHOR]

Introduction: One of the most serious complications associated with antiplatelet agents is antiplatelet‐associated intracranial hemorrhage (AA‐ICH). Desmopressin is a synthetic antidiuretic hormone (ADH) analog. It has been linked to improving patient outcomes in antiplatelet‐induced intracranial hemorrhage. The secondary outcomes included the incidence of thrombotic complications and neurological outcomes. Methods: A systematic search was conducted on three databases (PubMed, Cochrane, and ClinicalTrials.gov) to find eligible literature that compares desmopressin (DDAVP) versus controls in patients with AA‐ICH. The Mantel–Haenszel statistic was used to determine an overall effect estimate for each outcome by calculating the risk ratios and 95% confidence intervals (CI). Heterogeneity was measured using the I2 test. The risk of bias in studies was calculated using the New Castle Ottowa Scale. Results: Five studies were included in the analysis with a total of 598 patients. DDAVP was associated with a nonsignificant decrease in the risk of hematoma expansion (RR =.8, 95% CI,.51–1.24; p =.31, I2 = 44%). It was also associated with a non‐significant decrease in the risk of thrombotic events (RR,.83; 95% CI,.25–2.76; p =.76, I2 = 30%). However, patients in the DDAVP group demonstrated a significant increase in the risk of poor neurological outcomes (RR, 1.31; 95% CI, 1.07–1.61; p =.01, I2 = 0%). The risk of bias assessment showed a moderate to low level of risk. Conclusion: DDAVP was associated with a nonsignificant decrease in hematoma expansion and thrombotic events. However, it was also associated with a significantly poor neurological outcome in the patients. Thus, until more robust clinical trials are conducted, the use of DDAVP should be considered on a case‐to‐case basis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Comprehensive geriatric assessment (CGA) has been used in inpatient, outpatient, and emergency patients in Western countries and is an important evaluation tool in medicine. In China, the application of CGA to multiple single diseases has achieved satisfactory intervention effects. OBJECTIVE: To explore the effect of CGA on postoperative quality of life (QoL), psychological state, neurological recovery, and self-efficacy in patients with cerebral hemorrhage. METHODS: In this randomized controlled trial, a total of 133 postoperative patients with cerebral hemorrhage who were treated and nursed in our hospital between March 2019 and March 2021 were randomly assigned to a control group (68 patients) and an observation group (65 patients). The control group was given a general comprehensive care intervention. The observation group was evaluated using an electronic medical record-based CGA system that assessed patient prognosis and was given individualized interventions based on the CGA findings. The postoperative QoL, psychological state, neurological recovery, and self-efficacy of the two groups were compared. RESULTS: After the intervention, self-decompression, self-decision-making, and positive attitudes of the observation group were higher than those of the control group. However, the National Institute of Health Stroke Scale score of the observation group was lower than that of the control group, the Self-rating anxiety scale and self-rating depression scale scores of the observation group were lower than those of the control group, and the social support score was significantly higher in the observation group than in the control group. After the intervention, the mental vitality, social interaction, emotional restriction, and mental status scores of the observation group were significantly higher than those of the control group. CONCLUSION: Comprehensive evaluation of patients with cerebral hemorrhage based on a CGA, targeting the individual factors that affect the prognosis of patients, and formulating and implementing individualized nursing intervention programs based on the CGA results can effectively relieve the symptoms of cerebral hemorrhage, reduce anxiety and depression, and improve the QoL of patients with cerebral hemorrhage. [ABSTRACT FROM AUTHOR]

• Aphasia outcome is better in subcortical stroke as compared to cortical. • Intracerebral Hemorrhage has better aphasia outcome than Acute Ischemic Stroke. • FA of Arcuate Fasciculus has positive correlation with aphasia score while MD has negative correlation with the same. • Improvements in modified Rankin Scale and Aphasia scores are positively correlated. Aphasia is a language disorder acquired secondary to brain damage. This study aims to evaluate clinical and radiological profile of patients with post stroke aphasia and factors affecting its recovery. We conducted a prospective study of patients with first left Middle or Anterior Cerebral Artery infarct or Intracerebral Hemorrhage (ICH) with aphasia admitted within 14 days of stroke onset. Aphasia Quotient (AQ) was assessed at 2 weeks (AQ1) and 3 months (AQ2) using Western Aphasia Battery-Hindi version. Magnetic Resonance Imaging of brain with Diffusion Tensor Imaging (DTI) of bilateral Arcuate Fasciculus (AF) and Corticospinal Tract was done at admission, and stroke volume, Laterality Indices of Fractional Anisotropy (LI-FA), Mean Diffusivity (LI-MD), Radial Diffusivity (LI-RD), Axial Diffusivity (LI-AD) and Apparent Diffusion Coefficient (LI-ADC) were obtained. 36 patients [8 ICH and 28 Acute Ischemic Stroke (AIS)] were included. AQ1 and AQ2 were significantly higher in subcortical stroke than cortical. AQ2 and increase in AQ scores (including its subscores) were significantly higher in ICH than AIS. National Institutes of Health Stroke Scale score at admission and volume of stroke had significant negative correlation with AQ1 and AQ2. Laterality Index of Fractional Anisotropy of Arcuate Fasciculus [LI-FA (AF)] had significant positive correlation with AQ2 and naming score at 3 months. Laterality Index of Mean Diffusivity of Arcuate Fasciculus [LI-MD (AF)] had significant negative correlation with AQ1, AQ2 and all subcomponents of AQ2. Significant positive correlation was seen between improvements in Modified Rankin Scale score and AQ. The study shows that DTI can be used to predict severity of aphasia at follow up and recovery in language and motor functions occur in parallel [ABSTRACT FROM AUTHOR]

Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. We screened consecutive ICH patients (October 2012–December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101–9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046–0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557–3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124–6.162, p = 0.026). The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH. • Small ischemic lesions (SILs) with intracerebral hemorrhage affect prognosis. • We evaluated the impact of small-vessel disease on the development of SILs. • We also assessed the relation between polyunsaturated fatty acids and SILs. • Old lacunes and lower ω-3/ω-6 fatty-acid ratios were associated with SILs. • Pre-existing brain-vessel vulnerability and hypercoagulation might cause SILs. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), a common subtype of hemorrhagic stroke, often causes severe disability or death. ICH induces adverse events that might lead to secondary brain injury (SBI), and there is currently a lack of specific effective treatment strategies. To provide a new direction for SBI treatment post-ICH, the systematic review discussed how thrombin impacts secondary injury after ICH through several potentially deleterious or protective mechanisms. We included 39 studies and evaluated them using SYRCLE's ROB tool. Subsequently, we explored the potential molecular mechanisms of thrombin-mediated effects on SBI post-ICH in terms of inflammation, iron deposition, autophagy, and angiogenesis. Furthermore, we described the effects of thrombin in endothelial cells, astrocytes, pericytes, microglia, and neurons, as well as the harmful and beneficial effects of high and low thrombin concentrations on ICH. Finally, we concluded the current research status of thrombin therapy for ICH, which will provide a basis for the future clinical application of thrombin in the treatment of ICH. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. Methods: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. Results: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. Conclusions: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients. [ABSTRACT FROM AUTHOR]

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Objective: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Methods: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. Results: We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59--79), median baseline ICH volume 11.5 (IQR 4.3--28.9) mL, and median baseline CRP 2.5 (IQR 1.5--7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000--0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90--1.05, p = 0.51 and HR 0.98; 95%CI 0.93--1.03, p = 0.41, respectively). Conclusion: Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome. [ABSTRACT FROM AUTHOR]

Background and Aim: The prognostic potential of cardiac troponin (cTn) in acute stroke patients has been a subject of ongoing debate. Our objective was to provide a comprehensive evidence for predicting mortality in acute stroke patients by using the elevated troponin levels. Methods: We conducted an extensive literature search, including PubMed, EMbase, and Trip Databases, covering studies published up to September 30, 2023. We computed risk ratios (RR) with 95% confidence intervals (CIs), performed sensitivity analysis, and conducted trial sequential analysis (TSA). Results: In total, 53 studies were analyzed, with 37 focusing on acute ischemic stroke (AIS), 11 on subarachnoid hemorrhage (SAH), and 7 on Intracerebral hemorrhage (ICH). Elevated cTn levels were significantly showed a higher predictive risk for In-hospital mortality in both AIS (RR=3.80, 95% CI; 2.82 to 5.12) as well as SAH (RR=2.23, 95% CI; 1.64 to 3.02). However, no significant predictive risk between elevated cTn levels and in-hospital mortality for ICH patients (RR=1.13, 95% CI: 0.46 to 2.79). A similar pattern was observed for elevated cTn levels, indicating an increased risk of last follow-up mortality for AIS (RR=2.41, 95% CI: 1.98 to 2.93) and SAH (RR=3.08, 95% CI: 2.25 to 4.21). Conclusion: Elevated troponin levels can serve as a promising predictive marker for both in-hospital and last follow-up mortality in AIS and SAH patients but not in ICH patients. Further prospective studies are needed to validate our findings along with exploring the preventive management of mortality in acute stroke settings. [ABSTRACT FROM AUTHOR]

Introduction: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. Methods: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. Results: 291 were available for analysis under the trial’s modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8–18). The median baseline ICH volume was 12.9 IQR (6.4–26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. Conclusions: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration. [ABSTRACT FROM AUTHOR]

Homer1a and A2 astrocytes are involved in the regulation of inflammation induced by intracerebral hemorrhage (ICH). However, there is no anticipated treatment strategy based on the anti-inflammatory effect of Homer1a and A2 astrocytes. Here, we successfully induced A2 astrocytes in vitro, and then we report an efficient method to prepare Homer1a+ EVs derived from A2 astrocytes which making it more stable, safe, and targetable to injured neurons. Homer1a+ EVs promotes the conversion of A1 to A2 astrocytes in ICH mice. Homer1a+ EVs inhibits activation and nuclear translocation of NF-κB, thereby regulating transcription of IL-17A in neurons. Homer1a+ EVs inhibits the RAGE/NF-κB/IL-17 signaling pathway and the binding ability of IL-17A: IL17-AR and RAGE: DIAPH1. In addition, Homer1a+ EVs ameliorates the pathology, behavior, and survival rate in GFAPCreHomer1fl/−Homer1a± and NestinCreRAGEfl/fl ICH mice. Our study provides a novel insight and potential for the clinical translation of Homer1a+ EVs in the treatment of ICH. [ABSTRACT FROM AUTHOR]

This study examined the impact of vital signs and blood glucose levels on the long-term prognosis of intracerebral hemorrhage (ICH) patients treated with minimally invasive surgery (MIS). The patients diagnosed with ICH and treated with MIS within 24 hours of admission at the ∗∗ Hospital between January 2020 and October 2021 were included. The relationship between a range of indicators, including vital signs, blood glucose levels, and patient mortality at discharge and 3 or 12 months postdischarge were analyzed. A total of 195 consecutive patients were included, of which 16 patients passed away during hospitalization, 29 and 34 within 3 and 12 months postdischarge, respectively. The multivariate analysis revealed that hospital death positively correlated with age ≥66.50 years, fasting blood glucose ≥8.25 mmol/L on the third day after MIS, systolic blood pressure ≥166.00 mmHg on the third day, and heart rate ≥89.50 beats/min at discharge (area under the curve [AUC] = 0.927). Death at 3 months positively correlated with male sex, blood glucose before dinner ≥8.15 mmol/L on the second day after MIS, body temperature ≥36.95°C at discharge, and heart rate ≥89.50 beats/minute at discharge (AUC = 0.810). Death at 12 months positively correlated with age ≥61.50 years, body temperature ≥36.95°C at discharge, and heart rate ≥92.50 beats/min on the third day after MIS (AUC = 0.824). The prognosis of ICH patients after MIS is closely related to their vital signs and blood glucose levels at various stages of hospitalization. [ABSTRACT FROM AUTHOR]

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a "worst-case" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. Methods: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0–3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. Results: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). Conclusions: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH. Methods: We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast computed tomography images were analyzed for the presence of hypodensities according to validated criteria, defined as any hypodense region strictly encapsulated within the hemorrhage with any shape, size, and density. Occurrence of HE (defined as > 33% and/or > 6-mL growth) and mortality at 90 days were the outcomes of interest. Their predictors were investigated using logistic regression with backward elimination at p < 0.1. Logistic regression models for HE were adjusted for baseline ICH volume, antiplatelet and anticoagulant treatment, onset to computed tomography time, and presence of hypodensities. The logistic regression model for mortality accounted for the ICH score and HE. Results: A total of 175 patients were included (median age 75 years, 40.0% male), of whom 38 (21.7%) had HE and 43 (24.6%) died within 90 days. Study participants with HE had a higher frequency of hypodensities (44.7 vs. 24.1%, p = 0.013), presentation within 3 h from onset (39.5 vs. 24.8%, p = 0.029), and 90-day mortality (44.7 vs. 19.0%, p = 0.001). Hypodensities remained independently associated with HE after adjustment for confounders (odds ratio 2.44, 95% confidence interval 1.13–5.25, p = 0.023). The association between HE and mortality remained significant in logistic regression (odds ratio 3.68, 95% confidence interval 1.65–8.23, p = 0.001). Conclusion: Early presentation and presence of noncontrast computed tomography hypodensities were independent predictors of HE in infratentorial ICH, and the occurrence of HE had an independent prognostic impact in this population. [ABSTRACT FROM AUTHOR]

Background: Serum neutrophil–lymphocyte ratio (NLR) is a surrogate marker for the inflammatory response after intracerebral hemorrhage (ICH) and is associated with perihematomal edema and long-term functional outcomes. Whether NLR is associated with short-term ICH complications is poorly understood. We hypothesized that NLR is associated with 30-day infection and thrombotic events after ICH. Methods: We performed a post hoc exploratory analysis of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial. The study exposure was the serum NLR obtained at baseline and on days 3 and 5. The coprimary outcomes, ascertained at 30 days, were any infection and a thrombotic event, defined as composite of cerebral infarction, myocardial infarction, or venous thromboembolism; both infection and thrombotic event were determined through adjudicated adverse event reporting. Binary logistic regression was used to study the relationship between NLR and outcomes, after adjustment for demographics, ICH severity and location, and treatment randomization. Results: Among the 500 patients enrolled in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, we included 303 (60.6%) without missing data on differential white blood cell counts at baseline. There were no differences in demographics, comorbidities, or ICH severity between patients with and without data on NLR. In adjusted logistic regression models, NLR ascertained at baseline (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01–1.07, p = 0.03) and NLR ascertained at day 3 were associated with infection (OR 1.15; 95% CI 1.05–1.20, p = 0.001) but not with thrombotic events. Conversely, NLR at day 5 was associated with thrombotic events (OR 1.07, 95% CI 1.01–1.13, p = 0.03) but not with infection (OR 1.13; 95% CI 0.76–1.70, p = 0.56). NLR at baseline was not associated with either outcome. Conclusions: Serum NLR ascertained at baseline and on day 3 after randomization was associated with 30-day infection, whereas NLR obtained on day 5 was associated with thrombotic events after ICH, suggesting that NLR could be a potential early biomarker for ICH-related complications. [ABSTRACT FROM AUTHOR]

Background: Patients with intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) are at increased risk of developing epilepsy and cognitive disorders such as Alzheimer's disease (AD), mild cognitive impairment (MCI), and vascular dementia. In a retrospective cohort observation study of patients hospitalized for ICH with CAA versus ICH without CAA, we evaluated the prevalence of neurological comorbidities at admission and the risk of new diagnosis of epilepsy, relevant cognitive disorders, and mortality at 1 year. Methods: In the TriNetX health research network, adult patients aged ≥ 55 years hospitalized with a diagnosis of ICH were stratified based on presence or absence of concomitant CAA diagnosis. Demographics and medical comorbidities were compared by using χ2 test and Student's t-test. After 1:1 propensity score matching, 1-year survival was assessed with Kaplan–Meier curves. The 1-year risk of new diagnosis of epilepsy, AD, MCI, vascular dementia, and dementia unspecified was assessed with Cox proportional hazards estimate. Results: The study included a total of 1757 patients with ICH and CAA and 53,364 patients with ICH without CAA. Patients with CAA were older compared with those without CAA (74.1 ± 7.5 vs. 69.8 ± 8.8 years, p ≤ 0.001). Compared with ICH without CAA, patients with ICH and CAA had higher baseline prevalence of cerebral infarction (30% vs. 20%), nontraumatic ICH (36% vs. 7%), nontraumatic subarachnoid hemorrhage (14% vs. 5%), epilepsy (11% vs. 6%), and AD (5% vs. 2%) with significance at p < 0.001. After propensity score matching, a total of 1746 patients were included in both cohorts. In the matched cohorts, compared with patients with ICH without CAA, patients with ICH and CAA had lower 1-year all-cause mortality (479 [27%] vs. 563 [32%]; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.71–0.90) and higher risk of new diagnosis of epilepsy (280 [18%] vs. 167 [11%]; HR 1.70; 95% CI 1.40–2.06), AD (101 [6%] vs. 38 [2%]; HR 2.62; 95% CI 1.80–3.80), MCI (85 [5%] vs. 35 [2%]; HR 2.39; 95% CI 1.61–3.54), vascular dementia (117 [7%] vs. 60 [4%]; HR 1.92; 95% CI 1.41–2.62), and dementia unspecified (245 [16%] vs. 150 [9%]; HR 1.70; 95% CI 1.39–2.08). Conclusions: Among patients admitted for ICH, patients with CAA have lower mortality but have 2–3 times more risk of diagnosis of epilepsy and dementia at 1 year, compared with those without CAA. [ABSTRACT FROM AUTHOR]

Background: While it is thought that Borden Type I intracranial dural arteriovenous fistula (dAVF) have a benign clinical course, their management remains controversial. Methods: A comparative meta-analysis was completed to evaluate the outcomes of intervention verses observation of Borden Type I intracranial dAVF. Outcome measures included: grade progression, worsening symptoms, death due to dAVF, permanent complications other than death, functional independence (mRS 0–2), and rate of death combined with permanent complication, were evaluated. Risk differences (RD) were determined using a random effects model. Results: Three comparative studies combined with the authors' institutional experience resulted in a total of 469 patients, with 279 patients who underwent intervention and 190 who were observed. There was no significant difference in dAVF grade progression between the intervention and observation arms, 1.8% vs. 0.7%, respectively (RD: 0.01, 95% CI: −0.02 to 0.04, P = 0.49), or in symptom progression occurring in 31/279 (11.1%) intervention patients and 11/190 (5.8%) observation patients (RD: 0.03, CI: −0.02 to 0.09, P = 0.28). There was also no significant difference in functional independence on follow up. However, there was a significantly higher risk of dAVF related death, permanent complication from either intervention or dAVF related ICH or stroke in the intervention group (11/279, 3.9%) compared to the observation group (0/190, 0%) (RD: 0.04, CI: 0.1 to 0.06, P = 0.007). Conclusion: Intervention of Borden Type I dAVF results in a higher risk of death or permanent complication, which should be strongly considered when deciding on management of these lesions. [ABSTRACT FROM AUTHOR]

The microglia overactivation-induced neuroinflammation is a significant cause of the brain injury after intracerebral hemorrhage (ICH). Iron homeostasis is crucial for microglia activation, but the mechanism and causality still need further study. This study aimed to explore the roles and mechanism of the mitochondrial iron transporter SLC25A28 in microglia activation after ICH. Intrastriatal injection of autologous blood was used to establish ICH model, and the neuroinflammation, iron metabolism and brain injuries were assessed in wildtype or microglia-specific SLC25A28 knockout mice after ICH. Mitochondria iron levels and microglial function were determined in SLC25A28 overexpressed or deleted microglia. The extracellular acidification rate (ECAR), lactate production, and glycolytic enzyme levels were used to determine aerobic glycolysis. The results showed that ICH stimulated mitochondrial iron overload, and synchronously upregulated the SLC25A28 expression. In vitro, SLC25A28 overexpression increased mitochondrial iron levels in microglia. Interestingly, microglial SLC25A28 deficiency ameliorated neuroinflammation, brain edema, blood–brain barrier injury and ethological alterations in mice after ICH. Mechanically, SLC25A28 deficiency inhibited microglial activation by restricting the aerobic glycolysis. Moreover, zinc protoporphyrin could reduce SLC25A28 expression and mitigated brain injury. SLC25A28 plays crucial roles in mitochondrial iron homeostasis and microglia activation after ICH, and it might be a potential therapeutic target for ICH. [ABSTRACT FROM AUTHOR]

Purpose: In cases of acute intracerebral hemorrhage (ICH) volume estimation is of prognostic and therapeutic value following minimally invasive surgery (MIS). The ABC/2 method is widely used, but suffers from inaccuracies and is time consuming. Supervised machine learning using convolutional neural networks (CNN), trained on large datasets, is suitable for segmentation tasks in medical imaging. Our objective was to develop a CNN based machine learning model for the segmentation of ICH and of the drain and volumetry of ICH following MIS of acute supratentorial ICH on a relatively small dataset. Methods: Ninety two scans were assigned to training (n = 29 scans), validation (n = 4 scans) and testing (n = 59 scans) datasets. The mean age (SD) was 70 (± 13.56) years. Male patients were 36. A hierarchical, patch-based CNN for segmentation of ICH and drain was trained. Volume of ICH was calculated from the segmentation mask. Results: The best performing model achieved a Dice similarity coefficient of 0.86 and 0.91 for the ICH and drain respectively. Automated ICH volumetry yielded high agreement with ground truth (Intraclass correlation coefficient = 0.94 [95% CI: 0.91, 0.97]). Average difference in the ICH volume was 1.33 mL. Conclusion: Using a relatively small dataset, originating from different CT-scanners and with heterogeneous voxel dimensions, we applied a patch-based CNN framework and successfully developed a machine learning model, which accurately segments the intracerebral hemorrhage (ICH) and the drains. This provides automated and accurate volumetry of the bleeding in acute ICH treated with minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Objective: Neuronal precursor cells expressed developmentally down‐regulated 4 (Nedd4) are believed to play a critical role in promoting the degradation of substrate proteins and are involved in numerous biological processes. However, the role of Nedd4 in intracerebral hemorrhage (ICH) remains unknown. This study aims to investigate the regulatory role of Nedd4 in the ICH model. Methods: Male C57BL/6J mice were induced with ICH. Subsequently, the levels of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, as well as the expression of divalent metal transporter 1 (DMT1) and Nedd4 were assessed after ICH. Furthermore, the impact of Nedd4 overexpression was evaluated through analyses of hematoma area, ferroptosis, and neurobehavioral function. The mechanism underlying Nedd4‐mediated degradation of DMT1 was elecidated using immunoprecipitation (IP) after ICH. Results: Upon ICH, the level of DMT1 in the brain increased, but decreased when Nedd4 was overexpressed using Lentivirus, suggesting a negative correlation between Nedd4 and DMT1. Additionally, the degradation of DMT1 was inhibited after ICH. Furthermore, it was found that Nedd4 can interact with and ubiquitinate DMT1 at lysine residues 6, 69, and 277, facilitating the degradation of DMT1. Functional analysis indicated that overexpression of Nedd4 can alleviate ferroptosis and promote recovery following ICH. Conclusion: The results demonstrated that ferroptosis occurs via the Nedd4/DMT1 pathway during ICH, suggesting it potential as a valuable target to inhibit ferroptosis for the treatment of ICH. [ABSTRACT FROM AUTHOR]

Background: Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol‐requiring enzyme‐1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism. Methods: A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR‐25 and agomiR‐25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT‐qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed. Results: Endogenous phosphorylated IRE1α (p‐IRE1α), miR‐25‐3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR‐25‐3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR‐25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR‐25 reversed the effects promoted by KIRA6. Conclusion: The IRE1α phosphokinase activity is involved in the oxidative stress response through miR‐25/Nox4 pathway in the mouse ICH brain. [ABSTRACT FROM AUTHOR]

Laminin, a major component of the basal lamina in the CNS, is also expressed in oligodendrocytes (OLs). However, the function of OL-derived laminin remains largely unknown. Here, we performed loss-of-function studies using two OL-specific laminin-α5 conditional knockout mouse lines. Both mutants were grossly normal and displayed intact blood-brain barrier (BBB) integrity. In a mouse model of intracerebral hemorrhage (ICH), control mice and both mutants exhibited comparable hematoma size and neurological dysfunction. In addition, similar levels of hemoglobin and IgG leakage were detected in the mutant brains compared to the controls, indicating comparable BBB damage. Consistent with this finding, subsequent studies revealed no differences in tight junction protein (TJP) and caveolin-1 expression among control and knockout mice, suggesting that neither paracellular nor transcellular mechanism was affected in the mutants. Furthermore, compared to the controls, both mutant lines showed comparable oligodendrocyte number, oligodendrocyte proliferation rate, MBP/MAG levels, and SMI-32 expression, highlighting a minimal role of OL-derived laminin-α5 in OL biology. Together, these findings highlight a dispensable role of OL-derived laminin-α5 in both brain homeostasis and ICH pathogenesis. [ABSTRACT FROM AUTHOR]

Neuroinflammation and oxidative stress are critical players in intracerebral hemorrhage (ICH). Geniposide is an active component of Gardenia that has anti-inflammatory effects. This study focused on the roles and mechanisms of geniposide in ICH. ICH was established by injecting collagenase IV into C57BL/6 mice. To determine the functions of geniposide and NF-κB inhibition in ICH model mice, geniposide (1, 25, or 50 mg/kg) or PDTC (a NF-κB inhibitor) was administered. Neurological functions were assessed with the modified neurological severity score (mNSS) test. Hematoxylin and eosin staining were performed to identify pathological changes. IL-1β and TNF-α levels were estimated with ELISA kits. NF-κB p65 localization was determined by immunofluorescence staining. Oxidative stress was analyzed by measuring ROS levels. Geniposide alleviated cerebral edema and neurological deficits. Geniposide inhibited neuroinflammation and oxidative stress after ICH, and the inhibitory effects were enhanced by NF-κB inhibition. Additionally, geniposide inhibited NF-κB signaling. Geniposide alleviates brain injury by suppressing inflammation and oxidative stress damage in experimental ICH models by inhibiting NF-κB signaling. [ABSTRACT FROM AUTHOR]

Optic aphasia is a rare neurological disorder that affects the visual-semantic ability of patients with normal vision and is caused by a lesion in the left occipital lobe. The signs and symptoms of optic aphasia are similar to those of associative visual agnosia, where patients have difficulty recognizing objects both in shape and function, resulting in challenges performing daily tasks. The transformation to optic aphasia or associative visual agnosia is closely related to the degree of damage to the corpus callosum, with some studies hypothetically suggesting that complete damage to the corpus callosum leads to optic aphasia, whereas incomplete damage causes associative visual agnosia. We present a case of a 60-year-old man with a history of intracerebral hemorrhage in the left occipitotemporoparietal lobe. The patient complained of intermittent episodes of painless, blurry vision. Upon examination, we observed that the patient was unable to read the Snellen chart, although he could draw the letter. Furthermore, we discovered that the patient had difficulty naming objects and instruments, even though he was able to express their shape and function through gestures and mimicry. The signs and symptoms of the patient, along with the result of the multi-slice non-contrast CT scan, suggest that he had optic aphasia rather than associative visual agnosia. A comprehensive neuropsychological and aphasia examination needs to be performed to further assess the condition of our patient and establish the diagnosis. [ABSTRACT FROM AUTHOR]

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-β (Aβ) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aβ-clearing therapeutic agents such as taxifolin. [ABSTRACT FROM AUTHOR]

Objective: To evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF). Methods: We conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≥5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH. Results: We included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH--risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC. Conclusion: Anticoagulant therapy for ischemic stroke patients with nonvalvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS. [ABSTRACT FROM AUTHOR]

Systematic immune responses have been identified in patients with acute spontaneous intracerebral hemorrhage (ICH). T cells have been established to participate in central nervous system damage and repair following brain injury. However, their contribution to the prognosis of patients with ICH remains to be elucidated. In this study, peripheral blood mononuclear cells (PBMCs) were collected from 45 patients with acute spontaneous ICH (<24 h from symptom onset). Our results exposed significant negative correlations between hematoma volume/white blood cell (WBC) density and Glasgow Coma Scale (GCS) score. Contrastingly, lymphocyte density was negatively correlated with hematoma volume and positively correlated with GCS score. Moreover, flow cytometry determined that ICH activated T cells despite their proportion being lower in blood. Afterward, immune repertoire sequencing (IR-seq) revealed a significant decrease in VJ, VDJ usage, and TCR clonotypes in ICH patients. Finally, variations in the complementarity-determining region 3 (CDR3) amino acid (aa) were also detected in ICH patients. This study reveals the occurrence of peripheral T-cell diminishment and activation in response to acute hematoma. ICH lesion also alters the T cell receptor (TCR) immune repertoire, which is associated with patient prognosis. [ABSTRACT FROM AUTHOR]

To observe the preventive and therapeutic effects of resveratrol (Res) alone or in combination with miR-27b agonist on secondary pathological injury of brain tissues in rats with intracerebral hemorrhage (ICH) . Methods Totally 180 male SD rats were randomly divided into the sham-operated group, the ICH group, the Res group, the Res+miR-27b agomir group, and the NC group, with 36 rats in each group. The rats in the ICH group, the Res group, the Res+miR-27b agomir group, and the NC group were used to establish the ICH models by collagenase injection of the caudate nucleus method. Rats in the Res, Res+miR-27b agomir, and NC groups were injected intraperitoneally with Res for 7 consecutive days before modeling, while rats in the sham-operated and ICH groups were injected with an equal volume of DMSO. Rats in the Res+miR-27b agomir group were injected with the miR-27b agomir into the right ventricle of the rats for 3 d before modeling, while rats in the NC group were injected with agomir-negative control reagents. And rats in the sham operation, ICH, and Res groups were injected with equal volume of normal saline. After successful modeling, the rats in each group continued to receive feedings for 24 h. Neurological function was assessed by using the mNSS scoring scale. The brain tissues of rats in each group were taken after execution, and the apoptosis rate of neuronal cells in the brain tissues was measured by TUNEL method, while inflammatory factors and oxidative stress-related factors in the brain tissues of rats were detected by ELISA. Besides, qRT-PCR was used for the detection of miR-27b and nuclear factor-related factor 2（Nrf2) mRNA in the brain tissues of rats. Western blotting was used to detect the Nrf2/ARE signaling pathwayrelated proteins Nrf2, heme oxygenase (HO-1）, and quinone oxidoreductase 1（Nqo1) in the brain tissues of rats. Results The mNSS score, neuronal apoptosis rate of brain tissue, and the expression levels of TNF-α, IL-1β, and MDA in the sham-operated group were lower than those in the rest of the groups (all P<0. 05）, and the SOD activity was higher than those in the rest of groups (all P<0. 05) . The rat mNSS score, brain tissue neuronal cell apoptosis rate, and the expression levels of TNF-α, IL-1β, and MDA were higher in the ICH group than in the rest of groups (all P<0. 05）, and the SOD activity was lower than the rest of the groups (all P<0. 05) . Moreover, the mNSS score, apoptosis rate of neuronal cells in the brain tissue and the expression levels of TNF-α, IL-1β and MDA were higher in the Res+miR-27b agomir group than in the Res group and the NC group (all P<0. 05）, while the SOD vitality was lower than those in the Res group and the NC group (all P<0. 05) . Compared with the sham-operated group, the relative expression of miR-27b decreased in the brain tissues of rats in the ICH group, the Res group, the Res+miR-27b agomir group, and the NC group, whereas the relative expression of Nrf2 mRNA and protein, HO-1 protein, and NQO1 protein increased (all P<0. 05) . In comparison with the ICH group, the relative expression of miR-27b in the brain tissues of rats in the Res group, the Res+miR-27b agomir group, and the NC group decreased, while the relative expression of Nrf2 mRNA and protein, HO-1 protein, and NQO1 protein all increased (all P<0. 05) . Compared with the Res+miR-27b agomir group, the relative expression of miR27b decreased, while the relative expression levels of Nrf2 mRNA and protein, HO-1 protein, and NQO1 protein were elevated in the brain tissues of the rats in the Res group and the NC group (all P<0. 05) . Conclusion Res alone or in combination with miR-27b agomir has preventive effect on secondary pathological damage of brain tissue in rats with intracerebral hemorrhage, and this effect may be associated with the activation of the Nrf2/ARE signaling pathway. [ABSTRACT FROM AUTHOR]