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The benefits of exercise in TBI have been proven. However, the time-dependent effects of exercise initiation and the involved mechanisms are controversial. We investigated the effects of preconditioning, continuous, early, and delayed treadmill exercise on motor behavior, brain edema, inflammation, and oxidative stress in experimental traumatic brain injury (TBI). 48 male rats were assigned into two groups: sedentary control (Sham and TBI) and exercise groups: 1MB (preconditioning, initiation beginning at 1 month before trauma), 1MBA (continuous, initiation beginning at 1 month before and continuing 1 month after trauma), 24hA (early, initiation beginning at 24 h after trauma), and 1WA (delay, initiation beginning at 1 week after trauma). The rats in exercise groups were forced to run on a treadmill five days a week for 30 min per day. Rotarod and open file were used to assess motor behavior. ELISA was also used to measure total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) in serum and CSF. Exercise significantly decreased neurological impairments, motor deficits, and apoptosis compared with the sedentary group. Early (within 24 h) and ongoing (1 MBA) exercise significantly improved motor behavior after TBI. In addition, these exercise programs inhibited brain edema and the number of apoptotic cells. MDA and TNF-α levels increased in all exercise groups, but the effects were greater after early exercise than after delayed exercise, resulting in a significant decrease in TAC levels in serum and CSF. We discovered a positive correlation between MDA, TAC, and TNF-α concentration in serum and CSF. Our finding suggests that early exercise (24hA) and 1MBA groups afford neuroprotection and reduce the second injury consequence, probably by reducing neuronal apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

Ceftazidime/avibactam (CAZ/AVI) is a combination of a well‐known third‐generation, broad‐spectrum cephalosporin with a new beta‐lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug‐resistant Gram‐negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI‐related adverse events (AEs) in the real world through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities. The signals of CAZ/AVI‐related AEs were quantified using disproportionality analyses, including the reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network, and the multi‐item gamma Poisson shrinker algorithms. Out of 10,114,815 records retrieved from the FAERS database, 628 cases were identified, where CAZ/AVI was implicated as the primary suspect drug. A total of 61 preferred terms with significant disproportionality that simultaneously met the criteria of all four algorithms were retained. Several unexpected safety signals may also occur, including melena, hypernatremia, depressed level of consciousness, brain edema, petechiae, delirium, and shock hemorrhagic. The median onset time for AEs associated with CAZ/AVI was 4 days, with most cases occurring within 3 days after CAZ/AVI initiation. [ABSTRACT FROM AUTHOR]

Objective(s): Sox11, one of the SoxC family members, is an important transcription factor during neural development and neurogenesis. However, there is no report about its function in neural apoptosis. This research aims to examine the function of Sox11 in surgical brain injury (SBI). Materials and Methods: We used 90 Sprague-Dawley rats to develop the SBI models and the siRNA of Sox11 to study the roles of Sox11. Western blot, real-time PCR, immunofluorescence, neuron apoptosis and necrosis, brain edema, and neurological score were determined. Results: The gene and protein amount of Sox11, compared with the Sham group, were increased after SBI, which reached a peak at 12 hr. In addition, following the application of siRNAs, the amount of Sox11 protein was significantly less than that in the SBI group. On the other hand, neuronal apoptosis, necrosis, and brain edema were significantly increased, while neurological scores were decreased. Conclusion: These findings demonstrate the role of Sox11 following nerve injury induced by SBI. Inhibition of Sox11 with siRNA may lead to neuronal injury and cell death, aggravating secondary brain injury after SBI. [ABSTRACT FROM AUTHOR]

Background: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. Methods: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. Results: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = − 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = − 0.406, P = 0.026, PFDR = 0.026) scores. Conclusions: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection. [ABSTRACT FROM AUTHOR]

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ −0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers. [ABSTRACT FROM AUTHOR]

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics in the brain, impacting the development and resolution of edema following traumatic brain injury (TBI). This review examines the alterations in AQP expression and localization post-injury, exploring their effects on brain edema and overall injury outcomes. We discuss the underlying molecular mechanisms regulating AQP expression, highlighting potential therapeutic strategies to modulate AQP function. These insights provide a comprehensive understanding of AQPs in TBI and suggest novel approaches for improving clinical outcomes through targeted interventions. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In pediatrics, a leukemoid reaction in severe DKA cases with cerebral edema has never been reported. The fluid management was challenging as it required balancing rates to ensure improvement of the condition while preventing neurological sequelae. The combination of diabetic ketoacidosis (DKA), cerebral edema, and leukemoid reaction in pediatrics has never been reported before in the literature. It may lead to significant morbidity and high mortality. Here, we report a case of DKA‐induced cerebral edema associated with severe leukocytosis (WBC 98 × 109/L), which had many challenges in fluid therapy. [ABSTRACT FROM AUTHOR]

Background: Cerebral autoregulation is impaired early on after aneurysmal subarachnoid hemorrhage (aSAH). The study objective was to explore the pressure reactivity index (PRx) and cerebral perfusion pressure (CPP) in the earliest phase after aneurysm rupture and to address the question of whether an optimal CPP (CPPopt)–targeted management is associated with less severe early brain injury (EBI). Methods: Patients with aSAH admitted between 2012 and 2020 were retrospectively included in this observational cohort study. The PRx was calculated as a correlation coefficient between intracranial pressure and mean arterial pressure. By plotting the PRx versus CPP, CPP correlating the lowest PRx value was identified as CPPopt. EBI was assessed by applying the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) on day 3 after ictus. An SEBES ≥ 3 was considered severe EBI. Results: In 90 of 324 consecutive patients with aSAH, intracranial pressure monitoring was performed ≥ 7 days, allowing for PRx calculation and CPPopt determination. Severe EBI was associated with larger mean deviation of CPP from CPPopt 72 h after ictus (r = 0.22, p = 0.03). Progressive edema requiring decompressive hemicraniectomy was associated with larger deviation of CPP from CPPopt on day 2 (r = 0.23, p = 0.02). The higher the difference of CPP from CPPopt on day 3 the higher the mortality rate (r = 0.31, p = 0.04). Conclusions: Patients with CPP near to the calculated CPPopt in the early phase after aSAH experienced less severe EBI, less frequently received decompressive hemicraniectomy, and exhibited a lower mortality rate. A prospective evaluation of CPPopt-guided management starting in the first days after ictus is needed to confirm the clinical validity of this concept. [ABSTRACT FROM AUTHOR]

The purpose of this study was to describe the impact of enteral glyburide on cerebral edema formation and hypoglycemia when used to treat patients diagnosed with acute ischemic stroke (AIS). This study was a single-center, retrospective medical record review that included all patients aged ≥18 years diagnosed with AIS who received ≥1 dose of enteral glyburide for the prevention of cerebral edema from January 1, 2018 to March 31, 2022. The primary outcome was the percentage of patients requiring intervention for cerebral edema management after glyburide initiation, and the safety outcome was the occurrence of hypoglycemia in this patient population. The final evaluation included 44 patients, with 6 patients (14%) requiring intervention for cerebral edema after glyburide initiation. The average baseline National Institutes of Health stroke scale score was 19. Overall, in-hospital mortality was 36% (n = 17), and hypoglycemia occurred in 7 patients (15%). Of the 44 patients, 20 (45%) received a partial duration of enteral glyburide (1–4 doses) and 24 (55%) received a full duration of enteral glyburide (5–7 doses). The rate of intervention for cerebral edema (10% vs. 17%) and the incidence of hypoglycemia (5% vs. 23%) were lower in the partial duration than in the full duration group. The in-hospital all-cause mortality rate was higher in the partial duration group than in the full duration group (43% vs. 31%). Despite the relatively low rates of intervention for cerebral edema, hypoglycemia was common, especially for patients receiving 5–7 doses of enteral glyburide for the prevention of cerebral edema after moderate-to-severe AIS. [ABSTRACT FROM AUTHOR]

Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0–40.0). The median survival time after surgery was 5 months (IQR, 0.00–10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00–0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD. [ABSTRACT FROM AUTHOR]

Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague–Dawley rats were used, subjected to a collagenase‐induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test. Results indicated a significant improvement in neurological functions in loganin‐treated groups, evident from the mNSS and rotarod tests, suggesting dose‐dependent neuroprotection. Loganin also effectively reduced the blood–brain barrier (BBB) permeability and cerebral oedema. Additionally, it mitigated cellular pyroptosis, as shown by terminal deoxynucleotidyl transferase dUTP nick‐end labelling staining and western blot analysis, which indicated reduced levels of pyroptosis markers in treated rats. Furthermore, loganin's regulatory effects on the adenosine A2A receptor and myosin light chain kinase pathways were observed, potentially underpinning its protective mechanism against ICH. The study concludes that loganin exhibits significant neuroprotective properties in a rat ICH model, highlighting its potential as a novel therapeutic strategy. Despite promising results, the study needs further research to determine loganin's therapeutic potential in human ICH patients. This research paves the way for further exploration into loganin's clinical applications, potentially revolutionizing treatment strategies for patients suffering from intracerebral haemorrhage. [ABSTRACT FROM AUTHOR]

Autophagy is recognized as a promising therapeutic target for traumatic brain injury (TBI). Crocetin is an aglycone of crocin naturally occurring in saffron and has been found to alleviate brain injury diseases. However, whether crocetin affects autophagy after TBI remains unknown. Therefore, we explore crocetin roles in autophagy after TBI. We used a weight-dropped model to induce TBI in C57BL/6J mice. Neurological severity scoring (NSS) and grip tests were used to evaluate the neurological level of injury. Brain edema, neuronal apoptosis, neuroinflammation and autophagy were detected by measurements of brain water content, TUNEL staining, ELISA kits and western blotting. Crocetin ameliorated neurological dysfunctions and brain edema after TBI. Crocetin reduced neuronal apoptosis and neuroinflammation and enhanced autophagy after TBI. Crocetin alleviates TBI by inhibiting neuronal apoptosis and neuroinflammation and activating autophagy. [ABSTRACT FROM AUTHOR]

This review delves into updates in management of large hemispheric infarction (LHI), a condition affecting up to 10% of patients with supratentorial strokes. While traditional management paradigms have endured, recent strides in research have revolutionized the approach to acute therapies, monitoring, and treatment. Notably, advancements in triage methodologies and the application of both pharmacological and mechanical abortive procedures have reshaped the acute care trajectory for patients with LHI. Moreover, ongoing endeavors have sought to refine strategies for the optimal surveillance and mitigation of complications, notably space-occupying mass effect, which can ensue in the aftermath of LHI. By amalgamating contemporary guidelines with cutting-edge clinical trial findings, this review offers a comprehensive exploration of the current landscape of acute and ongoing patient care for LHI, illuminating the evolving strategies that underpin effective management in this critical clinical domain. [ABSTRACT FROM AUTHOR]

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood-brain barrier and to cerebral oedema after reperfusion therapy. The resulting fluid accumulation in the brain may contribute to a significant rise in intracranial pressure (ICP) and tissue deformation. Changes in the level of ICP are essential for clinical decision-making and therapeutic strategies. However, the measurement of ICP is constrained by clinical techniques and obtaining the exact values of the ICP has proven challenging. In this study, we propose the first computational model for the simulation of cerebral oedema following acute ischaemic stroke for the investigation of ICP and midline shift (MLS) relationship. The model consists of three components for the simulation of healthy blood flow, occluded blood flow and oedema, respectively. The healthy and occluded blood flow components are utilized to obtain oedema core geometry and then imported into the oedema model for the simulation of oedema growth. The simulation results of the model are compared with clinical data from 97 traumatic brain injury patients for the validation of major model parameters. Midline shift has been widely used for the diagnosis, clinical decision-making, and prognosis of oedema patients. Therefore, we focus on quantifying the relationship between ICP and midline shift (MLS) and identify the factors that can affect the ICP-MLS relationship. Three major factors are investigated, including the brain geometry, blood-brain barrier damage severity and the types of oedema (including rare types of oedema). Meanwhile, the two major types (stress and tension/compression) of mechanical brain damage are also presented and the differences in the stress, tension, and compression between the intraparenchymal and periventricular regions are discussed. This work helps to predict ICP precisely and therefore provides improved clinical guidance for the treatment of brain oedema. Author summary: Midline shift has been widely employed in clinical settings to estimate the severity of post-stroke brain oedema. However, the midline shift is affected by many factors and its relationship with intracranial pressure has been proven to vary among patients. In this paper, we utilise a computational tool to investigate the midline shift under large brain deformation from a mechanical perspective. The Augmented Lagrange Method is for the first time employed to solve the large deformation of oedema brains with midline shifts over 5 mm. In the model validation, a reasonable agreement between clinical data and simulation results are obtained. This paper models three different factors that can affect midline shift during oedema development, including brain geometry, blood-brain barrier damage severity and type of oedema. Meanwhile, we discuss the scenarios that can lead to unexpectedly small midline shifts and present quantitative results for a better understanding of brain mechanics during oedema. [ABSTRACT FROM AUTHOR]

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including (+)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated encephalopathy (SAE) causes acute and long-term cognitive deficits. However, information on the prevention and treatment of cognitive dysfunction after sepsis is limited. The neuropeptide orexin-A (OXA) has been shown to play a protective role against neurological diseases by modulating the inflammatory response through the activation of OXR1 and OXR2 receptors. However, the role of OXA in mediating the neuroprotective effects of SAE has not yet been reported. Methods: A mouse model of SAE was induced using cecal ligation perforation (CLP) and treated via intranasal administration of exogenous OXA after surgery. Mouse survival, in addition to cognitive and anxiety behaviors, were assessed. Changes in neurons, cerebral edema, blood-brain barrier (BBB) permeability, and brain ultrastructure were monitored. Levels of pro-inflammatory factors (IL-1β, TNF-α) and microglial activation were also measured. The underlying molecular mechanisms were investigated by proteomics analysis and western blotting. Results: Intranasal OXA treatment reduced mortality, ameliorated cognitive and emotional deficits, and attenuated cerebral edema, BBB disruption, and ultrastructural brain damage in mice. In addition, OXA significantly reduced the expression of the pro-inflammatory factors IL-1β and TNF-α, and inhibited microglial activation. In addition, OXA downregulated the expression of the Rras and RAS proteins, and reduced the phosphorylation of P-38 and JNK, thus inhibiting activation of the MAPK pathway. JNJ-10,397,049 (an OXR2 blocker) reversed the effect of OXA, whereas SB-334,867 (an OXR1 blocker) did not. Conclusion: This study demonstrated that the intranasal administration of moderate amounts of OXA protects the BBB and inhibits the activation of the OXR2/RAS/MAPK pathway to attenuate the outcome of SAE, suggesting that OXA may be a promising therapeutic approach for the management of SAE. [ABSTRACT FROM AUTHOR]

Background: Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood–brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans. Methods: Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH. Results: The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH. Conclusion: Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients. [ABSTRACT FROM AUTHOR]

• A systematic review of the pathophysiologic processes of SAH was conducted. • The role of natural compounds in the pathophysiologic process of SAH. • Signaling pathway mechanisms by which natural compounds act in SAH. • Natural compounds are categorized in detail. • Evaluate the prognostic potential of natural compounds to improve SAH. Subarachnoid hemorrhage (SAH) is a common and fatal cerebrovascular disease with high morbidity, mortality and very poor prognosis worldwide. SAH can induce a complex series of pathophysiological processes, and the main factors affecting its prognosis are early brain injury (EBI) and delayed cerebral ischemia (DCI). The pathophysiological features of EBI mainly include intense neuroinflammation, oxidative stress, neuronal cell death, mitochondrial dysfunction and brain edema, while DCI is characterized by delayed onset ischemic neurological deficits and cerebral vasospasm (CVS). Despite much exploration in people to improve the prognostic outcome of SAH, effective treatment strategies are still lacking. In recent years, numerous studies have shown that natural compounds of plant origin have unique neuro- and vascular protective effects in EBI and DCI after SAH and long-term neurological deficits, which mainly include inhibition of inflammatory response, reduction of oxidative stress, anti-apoptosis, and improvement of blood–brain barrier and cerebral vasospasm. The aim of this paper is to systematically explore the processes of neuroinflammation, oxidative stress, and apoptosis in SAH, and to summarize natural compounds as potential targets for improving the prognosis of SAH and their related mechanisms of action for future therapies. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), recognized as the world's most serious public health problem, currently lacks effective treatment options. The development of the patch has great clinical significance whether it is used as a skull implant material or TBI repair. In response to this critical health challenge, a novel 3D‐printed bi‐layer cranial‐brain patch (SMB6) with dual functionality, addressing both TBI repair and skull regeneration, is developed. In the first layer, the incorporation of high concentrations of mesoporous bioactive glass nanoparticles establishes a microenvironment for bone regeneration. Meanwhile, the second layer, comprised of methacrylated silk fibroin hydrogel, provides essential mechanical support for nanocell membrane vesicles loaded with macrophage colony‐stimulating factor and interleukin‐6. This innovative design aims to interrupt the cascade of secondary brain injury. In experimental models of TBI, SMB6 demonstrates remarkable efficacy in inhibiting brain edema, exerting therapeutic effects on blood vessels, nerves, and inflammation. Additionally, promising outcomes are observed in promoting bone regeneration in skull defect models. This work not only introduces a potential therapeutic patch for TBI‐related diseases but also provides novel insights for the clinical translation of cranial patches. [ABSTRACT FROM AUTHOR]

Objective: To establish whether or not a natural language processing technique could identify two common inpatient neurosurgical comorbidities using only text reports of inpatient head imaging. Materials and methods: A training and testing dataset of reports of 979 CT or MRI scans of the brain for patients admitted to the neurosurgery service of a single hospital in June 2021 or to the Emergency Department between July 1–8, 2021, was identified. A variety of machine learning and deep learning algorithms utilizing natural language processing were trained on the training set (84% of the total cohort) and tested on the remaining images. A subset comparison cohort (n = 76) was then assessed to compare output of the best algorithm against real-life inpatient documentation. Results: For "brain compression", a random forest classifier outperformed other candidate algorithms with an accuracy of 0.81 and area under the curve of 0.90 in the testing dataset. For "brain edema", a random forest classifier again outperformed other candidate algorithms with an accuracy of 0.92 and AUC of 0.94 in the testing dataset. In the provider comparison dataset, for "brain compression," the random forest algorithm demonstrated better accuracy (0.76 vs 0.70) and sensitivity (0.73 vs 0.43) than provider documentation. For "brain edema," the algorithm again demonstrated better accuracy (0.92 vs 0.84) and AUC (0.45 vs 0.09) than provider documentation. Discussion: A natural language processing-based machine learning algorithm can reliably and reproducibly identify selected common neurosurgical comorbidities from radiology reports. Conclusion: This result may justify the use of machine learning-based decision support to augment provider documentation. [ABSTRACT FROM AUTHOR]

Sodium valproate overdose leads to CNS depression, cerebral oedema, and severe metabolic acidosis in cases of severe toxicity. Extracorporeal removal, specifically through intermittent haemodialysis, is recommended, though not always tolerated by or accessible to haemodynamically unstable patients in intensive care units. We present a case of a male in his mid-twenties presenting following a massive, intentional overdose of 13 g of sodium valproate over 7 hours, with an initial valproate blood concentration of 975 μg/ml (normal 50-100 μg/ml). He was hypoxic and severely acidotic on arrival and was given fluids and L-carnitine according to TOXBASE guidelines. This resulted in only marginal improvement to his acidosis. Once transferred to our intensive care unit, the patient was started on inotropic support followed by continuous venovenous hemofiltration (CVVHDF) at the maximum effluent rate of 60 ml/kg/hr. Due to his persisting metabolic acidosis and worsening hyperlacataemia, dual CVVHDF was started by adding another filter in series after 26 hours, increasing the maximum effluent rate to 96 ml/kg/hr. The patient remained on dual CVVHDF for 31 hours, during which his acidosis and lactate showed considerable improvement, and he was subsequently stepped down to single-filter CVVHDF for a further 20 hours until complete resolution of his acidosis. This case report recognises dual CVVHDF as a viable salvage therapy for severe sodium valproate overdose by facilitating the achievement of a higher effluent flow rate compared to what can be accomplished with single-filter CVVHDF. [ABSTRACT FROM AUTHOR]

Objective: Management of emergency care Background: Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. Case Report: A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). Conclusions: Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. Methods: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. Results: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. Conclusion: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways. [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]

Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation or even death. Current treatment strategies are limited to decompressive craniectomy and the intravascular administration of hypertonic drugs, which have significant side effects. Acetazolamide (ACZ) plays a therapeutic role in cerebral edema by inhibiting aquaporin-4 (AQP-4) and improving collateral circulation. This study aimed to perform a meta-analysis and systematic review of ACZ therapy for ischemic stroke and evaluate its efficacy in animal models. We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke. After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, −2.00; 95% confidence interval, −3.57 to −0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference−1.46; 95% confidence interval, −2.01 to −0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals' neurological function is uncertain because of the limited research data. ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function. [ABSTRACT FROM AUTHOR]

Background: Stroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood–brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment. Results: Synaptic dysfunction occurs in various ways after stroke and includes the following: damage to neuronal structures, accumulation of pathologic proteins in the cell body, decreased fluidity and release of synaptic vesicles, disruption of mitochondrial transport in synapses, activation of synaptic phagocytosis by microglia/macrophages and astrocytes, and a reduction in synapse formation. Conclusions: This review summarizes the cellular and molecular mechanisms related to synapses and the protective effects of drugs or compounds and rehabilitation therapy on synapses in stroke according to recent research. Such an exploration will help to elucidate the relationship between stroke and synaptic damage and provide new insights into protecting synapses and restoring neurologic function. [ABSTRACT FROM AUTHOR]

This study aimed to assess the therapeutic efficacy of neuroendoscopic minimally invasive surgery combined with mannitol and furosemide for treating hypertensive intracerebral hemorrhage. We retrospectively analyzed clinical data from 200 patients with hypertensive intracerebral hemorrhage treated at our hospital between July 2020 and July 2022. The patients were categorized into either the experimental group (undergoing neuroendoscopic minimally invasive surgery combined with mannitol and furosemide) or the control group (undergoing neuroendoscopic minimally invasive surgery alone). Then, we compared the efficacy and impact on patients between the two groups. After treatment, the experimental group exhibited a smaller edema area compared to the control group and a reduced hematoma volume (p < 0.001). The total effective rate was significantly higher in the experimental group compared to the control group (p < 0.05). At 7 days post-treatment, patients in the experimental group demonstrated a significantly lower National Institutes of Health Stroke Scale (NIHSS) score compared to the control group (p < 0.001). Additionally, 3 and 7 days after treatment, levels of lipid peroxidation (LPO), neuron-specific enolase (NSE), and S-100ß were significantly lower in the experimental group compared to the control group (p < 0.001). Similarly, carotid total blood flow volume (Q) and blood flow velocity (V) were significantly higher in the experimental group at 3 and 7 days post-treatment, with lower peripheral resistance (R) compared to the control group (p < 0.001). The incidence rate of complications was significantly lower in the experimental group compared to the control group (p < 0.05). The integration of neuroendoscopic minimally invasive surgery with mannitol and furosemide administration demonstrates potential in alleviating brain edema, reducing related cytokine levels, facilitating neurological function recovery, and improving cerebral hemodynamic parameters in hypertensive intracerebral hemorrhage patients. These findings merit clinical promotion and application. [ABSTRACT FROM AUTHOR]

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46–12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92–3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions. [ABSTRACT FROM AUTHOR]

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]

This document is an editorial from the Journal of Clinical Medicine that introduces a special issue dedicated to addressing the challenges in the management of cerebral aneurysms (CA). The special issue includes ten publications covering various topics related to the diagnosis and treatment of CA. The editorial highlights the importance of early recognition of complications after subarachnoid hemorrhage (SAH) and the need for individualized treatment approaches. It also emphasizes the significance of precise patient selection for preventive interventions and efforts to improve treatment outcomes. The document provides a list of the contributions included in the special issue. [Extracted from the article]

Background: The purpose of this study was to evaluate the ability of intraoperative ultrasound (IOUS) to differentiate the gross pathological features of brain mass lesions in comparison with preoperative imaging and confirmable histopathological results. Results: A total of 365 patients were operated on for brain mass lesions removal from May 2017 to May 2022 under the guidance of intraoperative ultrasound with transducers 2.5–8 megahertz (MHZ). Ultrasound gross pathological findings were compared to the preoperative imaging and the confirmable histopathological results. Intraoperative ultrasound defined either internal or external gross pathological features of all brain mass lesions. The IOUS showed spontaneous enhancements of the brain abscess walls, which were equivalent to contrasted CT and MRI. Significantly large diameters were noted in the IOUS measurement of abscesses in comparison with CT and MRI (P = 0.001). The walls of the brain abscesses were significantly well defined in IOUS imaging in comparison with CT (P = 0.001) and equivalent to MRI. IOUS showed equivalent significance to CT and MRI in characterizing intra-parenchymal hematomas. Significantly large diameters were noted in the IOUS measurement of hematomas in comparison with CT and MRI (P = 0.001). IOUS showed significant definition of brain tumors in comparison with CT and MRI regarding tumor edge definition, tumor contours, necrosis, and cystic components (cystic definition, cystic multiplicity, cystic trabeculations, and cystic wall thickness) (P = 0.001). IOUS was equivalent to CT and MRI regarding intra-tumoral hematomas and brain edema. IOUS was equivalent to CT regarding calcification detection. The significant criteria for high-grade brain tumors versus low grade by IOUS were: P = 0.001 (necrosis, brain edema, rare calcifications, presence of cystic components, thick cystic walls, large diameter, hypo-echogenicity, and heterogeneity); P = 0.002 (cystic trabeculations); P = 0.005 (multiple cysts); and P = 0.03 (irregular contour). IOUS can characterize brain tumors and suspect specific and significant criteria for many types with great overlap. Conclusions: Intraoperative ultrasound has the ability to differentiate the gross pathological features of brain mass lesions in comparison with preoperative imaging and confirmable histopathological results. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatic encephalopathy (HE) is a major neurological condition that occurs following acute or chronic liver failure. There are two types of HE: acute (Type A) and chronic (Type C). The acute form leads to rapid coma and death due to increased intracranial pressure, while neurobehavioral abnormalities potentially characterize the chronic form. There is currently no available treatment to regress or cure HE. This may be due to various factors, of which age and sex are the most important to consider when treating patients with HE. Accordingly, we examined whether sex and age play a role in the development of HE. We found that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. Furthermore, adding alcohol to the young male or young/aged female rats aggravated the brain edema. Regarding the behavioral changes, TAA-induced deficits were less pronounced in young and aged females than in aged males, whereas in the chronic type, young and aged males showed no behavioral changes when alcohol was infused along with TAA despite the severe brain edema and death that occurred. These findings suggest that aged males and young/aged females are more prone to developing brain edema in the presence of one or more liver toxins. Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression. [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]

To identify risk factors associated with in-hospital seizures and new-onset epilepsy in patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent coiling embolization or clipping surgery. This retrospective descriptive study included 195 patients diagnosed with aneurysmal SAH and treated with coiling embolization or clipping surgery between January 2018 and June 2022. Among the 195 patients meeting inclusion criteria, 9 experienced an onset seizure at the time of SAH. In-hospital seizures were observed in 33 patients, of which 24 were electrographic seizures detected in 24 patients with suspected subclinical seizures. After 12 months of follow-up, 11 patients met criteria for diagnosis of epilepsy. The incidence of epilepsy after discharge at 12 months was 2.41% in the coiling group and 8.03% in the clipping group. The risk of in-hospital seizures was significantly higher in the clipping group (P = 0.007), although the difference was not statistically significant after 12 months of follow-up (P = 0.121). Epilepsy following aneurysmal SAH was relatively common. Clipping surgery and brain edema emerged as independent predictive factors for in-hospital seizures, while onset seizures and in-hospital seizures were identified as independent predictors of epilepsy during follow-up. Patients presenting with these risk factors may benefit from long-term electroencephalogram monitoring and should be considered for prophylactic antiepileptic drugs. Additionally, lumbar drainage proved effective in improving both early and late epileptic outcomes in the group with Fisher grades 3 and 4. [ABSTRACT FROM AUTHOR]

The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia. [ABSTRACT FROM AUTHOR]

Objectives: Liver cirrhosis patients commonly progress to minimal hepatic encephalopathy (MHE) with cognitive impairment and raised blood ammonia and proinflammatory cytokines levels. This study aims to identify the subjects of MHE in patients with liver cirrhosis by hydrogen 1 magnetic resonance (¹H-MR) spectroscopy of the brain, serum proinflammatory cytokines, and neuropsychiatric tests. Materials and Methods: This prospective was carried out on 100 patients of liver cirrhosis without overt hepatic encephalopathy (HE) and compared with 100 healthy controls in a tertiary care hospital in Northeast India between September 2017 and October 2019. The psychometric hepatic encephalopathy score (PHES) neuropsychological tests, cranial MRIwith ¹H-MR spectroscopy, and estimation of serum interleukin 6 (IL-6) and tumor necrosis factoralpha (TNF-α) were done. The PHES scores and serum proinflammatory markers levels were correlated with the conventional and ¹H-MR spectroscopy findings of the brain. Results: The mean PHES score in the case group was -7.58±3.43 (standard deviation [SD]) and the control group was -3.41 ± 3.87 (SD). Patients with Child-Pugh class A (n = 8) had a PHES score of -8.7 ± 2.5 (SD), class B (n = 42) -7.62 ± 3.7 (SD), and class C (n = 50) had a score of -7.36 ± 3.3 (SD). The mean value of IL-6 and TNF-α in the case group was 219 ± 180 (SD) pg/mL and 99 ± 118 (SD) pg/mL and the control group was 67.4 ± 77 (SD) pg/mL and 57.5 ± 76 (SD) pg/mL. Globus pallidus T1-weighted hyperintensities on the visibility scale with a visibility score of 0 were observed in 39 cases, a score of 1 in 38 cases, and a score of 2 in 23 cases. Increased glutamate/glutamine/creatine (Glx/Cr) ratio was identified in the case group on MR spectroscopy as compared to the control (0.95 ± 0.24 vs. 0.31 ± 0.19, P < 0.0005), a decrease of myoinositol/creatine (mI/Cr) ratio (0.11 ± 0.13 vs. 0.30 ± 0.12, P < 0.0005), and increase choline/creatine (Cho/Cr) ratio (0.69 ± 0.26 vs. 0.61 ± 0.20, P < 0.0005). There was a statistically significant difference in Glx/Cr, mI/Cr and Cho/Cr ratio between the case and control groups with P < 0.0005. Conclusion: Predicting the development of MHE in established cases of liver cirrhosis using non-invasive modalities like PHES, IL-6, TNF-α levels, and ¹H-MR spectroscopy plays an important role in further progression to overt HE and coma. [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]

Traumatic brain injuries represent a leading cause of death and disability in the paediatric and adult populations. Moderate-to-severe injuries are associated with blood–brain barrier dysfunction, the development of cerebral oedema, and neuroinflammation. Antagonists of the tachykinin NK1 receptor have been proposed as potential agents for the post-injury treatment of TBI. We report on the identification of EUC-001 as a potential clinical candidate for development as a novel TBI therapy. EUC-001 is a selective NK1 antagonist with a high affinity for the human NK1 receptor (Ki 5.75 × 10−10 M). It has sufficient aqueous solubility to enable intravenous administration, whilst still retaining good CNS penetration as evidenced by its ability to inhibit the gerbil foot-tapping response. Using an animal model of TBI, the post-injury administration of EUC-001 was shown to restore BBB function in a dose-dependent manner. EUC-001 was also able to ameliorate cerebral oedema. These effects were associated with a significant reduction in post-TBI mortality. In addition, EUC-001 was able to significantly reduce functional deficits, both motor and cognitive, that normally follow a severe injury. EUC-001 is proposed as an ideal candidate for clinical development for TBI. [ABSTRACT FROM AUTHOR]

Background. Central neurocytoma is a benign intraventricular neuroectodermal tumor most often arising in the lateral ventricles. Due to the location of this tumor, common signs and symptoms include obstructive hydrocephalus, recurrent headache, visual impairment, nausea, and vomiting. Central neurocytoma and intraventricular oligodendroglioma share similar gross features and cellular and architectural morphology, which may pose a diagnostic challenge in a poor resource setting. Immunohistochemical neuronal stains are useful for the two tumors in our setting. Report. An 18-year-old male patient presented with a 1-year history of right-sided weakness, recurrent seizures, and sudden loss of consciousness. The patient showed signs of increased intracranial pressure, but an antemortem CT or MRI scan could not be done to determine the underlying cause, due to lack of availability and poor prognosis of the patient at the time of presentation. An autopsy revealed a well-demarcated solid cystic, gritty intraventricular tumor causing obstructive hydrocephalus, with associated dilated ventricles and severe cerebral edema. Postmortem histopathological examination of the tumor confirmed central neurocytoma. Conclusion. Central neurocytoma (CN) is an uncommon cause of intracranial space occupying lesion (ICSOL) in the teenage age group in our setting. Central neurocytoma and intraventricular oligodendroglioma share similar radiologic and histomorphological features. Immunohistochemical evaluation with neuronal markers is essential in these two tumors, as they have different prognoses and surgical and treatment outcomes. [ABSTRACT FROM AUTHOR]

Currently, with the knowledge of the role of collateral circulation in the development of cerebral ischaemia, traditional therapeutic windows are being prolonged, with time not being the only criterion. Instead, a more personalised approach is applied to select additional patients who might benefit from active treatment. This review briefly describes the current knowledge of the pathophysiology of the development of early ischaemic changes, the capabilities of MRI to depict such changes, and the basics of the routinely used imaging techniques broadly available for the assessment of individual phases of cerebral ischaemia, and summarises the possible clinical use of routine MR imaging, including patient selection for active treatment and assessment of the outcome on the basis of imaging. [ABSTRACT FROM AUTHOR]

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. Methods: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. Results: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). Conclusions: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA. [ABSTRACT FROM AUTHOR]

Sevoflurane has become an important volatile anesthetic in clinic and has been widely studied in recent years. Numerous studies have demonstrated the efficacy of sevoflurane in safeguarding against brain damage across various domains. For example, it has played a neuroprotective role in subarachnoid hemorrhage (SAH), traumatic brain injury, and ischemia/reperfusion injury. The ensuing critique will focus on the significance of sevoflurane in experimental SAH and shed light on the underlying mechanisms. The findings of the current investigation demonstrate that sevoflurane possesses neuroprotective capabilities and clarify that it effectively attenuates secondary damage resulting from SAH through anti-inflammatory and anti-apoptotic pathways. More specifically, sevoflurane is observed to mitigate arterial vasospasm, diminish microvascular thrombosis, and alleviate cerebral edema. In light of these discoveries, we maintain that sevoflurane exhibits significant promise in the management of SAH, and it merits additional investigation to facilitate its prompt clinical implementation. Therefore, a thorough understanding of the neuroprotective properties of sevoflurane is beneficial to exploring novel therapeutic solutions for SAH and providing clinicians with alternative treatment modalities. [ABSTRACT FROM AUTHOR]

We assessed the effectiveness and safety of target temperature management (TTM) in treating patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). The primary objective was to evaluate the neurological outcome at 3 months. Secondary objectives were to assess mortality, delayed cerebral ischemia, cerebral edema, hydrocephalus, midline shift, and laboratory indicators related to TTM. A single-blind, nonrandomized controlled trial was conducted. After admission, patients with poor-grade aSAH (Hunt-Hess scores IV ∼ V) were assigned to a TTM group or a control group in a 1:1 ratio. TTM with core temperatures ranging from 36°C to 37°C was performed immediately and maintained until microclipping or endovascular embolization. Subsequently, rapid induction to 33°C ∼ 35°C was carried out and maintained for 3 to 5 days. Then, the patients underwent slow rewarming to 36°C ∼ 37°C and maintained at that temperature for a minimum of 48 hours. Sixty patients (30 treated with TTM and 30 with standard treatment) were included in the study. At 3 months, a favorable prognosis (modified Rankin scale score 0 to 3) was significantly higher in the TTM group than in the control group (n = 14, 46.7% vs. n = 6, 20.0%, P = 0.028). Adjusted multivariate logistics regression analysis indicated that TTM (odds ratio = 0.20, 95% confidence interval: 0.05–0.77, P = 0.019) reduced the number of unfavorable prognoses 3 months after admission. This study demonstrated the effectiveness and safety of TTM in patients with poor-grade aSAH, and its implementation improved neurological outcomes. Multicenter randomized controlled studies with a large number of patients are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

After craniectomy, autologous bone flaps may be stored using wet or dry cryopreservation. After brain edema subsides, they are replaced during an operation termed cranioplasty. Cranioplasty is associated with 15% infection incidence. We conducted a retrospective comparison of infection outcomes between wet and dry cryopreservation of cranioplasty bone flaps. Historically, bone flaps were stored utilizing wet cryopreservation—bone flap storage in 1 L of lactated Ringer's solution containing 80 mg gentamicin and 2 g nafcillin in a sterile plastic container secured in an unsterile plastic bag. Our newer dry cryopreservation protocol involved storage in gauze soaked in 80 mg gentamicin and 2 g nafcillin within a 3-layer sterile bag system. A total of 119 autologous bone flaps were included, with median follow-up of 3.9 months from cranioplasty. Overall, 10.9% became infected, requiring subsequent surgery; 18.4% of 49 bone flaps stored using wet cryopreservation became infected compared with only 5.7% of 70 dry cryopreservation bone flaps (P = 0.038; relative risk [RR] 0.311; absolute risk reduction 12.7%). Tobacco use (P = 0.076; RR 3.17) was not associated with increased infection risk. Infection incidence was similar for traumatic craniectomy indications compared to the other indications (12.0% trauma vs. 10.1% other; P = 0.750). On average, infected cranioplasty patients spent 8.5 more days hospitalized and faced increased risk of additional complications. Dry cryopreservation significantly decreases infection after cranioplasty when compared with wet cryopreservation, and this mitigates additional morbidity, mortality, and costs attributable to cranioplasty infection. Other nonmodifiable risk factors for cranioplasty infection were identified. [ABSTRACT FROM AUTHOR]

Studies suggest that both genomic and nongenomic pathways are involved in mediating the salutary effects of steroids following traumatic brain injury (TBI). This study investigated the nongenomic effects of 17β-estradiol (E2) mediated by the PI3K/p-Akt pathway after TBI. Ovariectomized rats were apportioned to E2, E2-BSA (E2 conjugated to bovine serum albumin), G1 [G-protein-coupled estrogen receptor agonist (GPER)] or their vehicle was injected following TBI, whereas ICI (classical estrogen receptor antagonist), G15 (GPER antagonist), ICI + G15, and their vehicles were injected before the induction of TBI and injection of drugs. Diffuse TBI was induced by the Marmarou model. Evans blue (EBC, 5 h), brain water contents (BWC), histopathological changes, and brain PI3K and p-Akt protein expressions were measured 24 h after TBI. The veterinary comma scale (VCS) was assessed before and at different times after TBI. The results showed a reduction in BWC and EBC and increased VCS in the E2, E2-BSA, and G1 groups. Also, E2, E2-BSA, and G1 reduced brain edema, inflammation, and apoptosis. The ICI and G15 inhibited the beneficial effects of E2, E2-BSA, and G1 on these parameters. All drugs, following TBI, prevented the reduction of brain PI3K/p-Akt expression. The individual or combined use of ICI and G15 eliminated the beneficial effects of E2, E2-BSA, and G1 on PI3K/p-Akt expressions. These findings indicated that PI3K/p-Akt pathway plays a critical role in mediating the salutary effects of estradiol on histopathological changes and neurological outcomes following TBI, suggesting that GPER and classic ERs are involved in regulating the expression of PI3K/p-Akt. [ABSTRACT FROM AUTHOR]

Objective: Numerous studies have indicated that early decompressive craniectomy (DC) for patients with major infarction can be life-saving and enhance neurological outcomes. However, most of these studies were conducted by neurologists before the advent of intra-arterial thrombectomy (IA-Tx). This study aims to determine whether neurological status significantly impacts the final clinical outcome of patients who underwent DC following IA-Tx in major infarction. Methods: This analysis included 67 patients with major anterior circulation major infarction who underwent DC after IA-Tx, with or without intravenous tissue plasminogen activator. We retrospectively reviewed the medical records, radiological findings, and compared the neurological outcomes based on the "surgical time window" and neurological status at the time of surgery. Results: For patients treated with DC following IA-Tx, a Glasgow coma scale (GCS) score of 7 was the lowest score correlated with a favorable outcome (p=0.013). Favorable outcomes were significantly associated with successful recanalization after IA-Tx (p=0.001) and perfusion/diffusion (P/D)-mismatch evident on magnetic resonance imaging performed immediately prior to IA-Tx (p=0.007). However, the surgical time window (within 36 hours, p=0.389; within 48 hours, p=0.283) did not correlate with neurological outcomes. Conclusion: To date, early DC surgery after major infarction is crucial for patient outcomes. However, this study suggests that the indication for DC following IA-Tx should include neurological status (GCS ≤7), as some patients treated with early DC without considering the neurological status may undergo unnecessary surgery. Recanalization of the occluded vessel and P/D-mismatch are important for long-term neurological outcomes. [ABSTRACT FROM AUTHOR]

Purpose Metabolic abnormalities in hepatic encephalopathy (HE) cause brain edema or demyelinating disease, resulting in symmetric regional cerebral edema (SRCE) on MRI. This study aimed to investigate the usefulness of the clustering analysis of SRCE in predicting the development of brain failure. Materials and Methods MR findings and clinical data of 98 consecutive patients with HE were retrospectively analyzed. The correlation between the 12 regions of SRCE was calculated using the phi (φ) coefficient, and the pattern was classified using hierarchical clustering using the φ2 distance measure and Ward's method. The classified patterns of SRCE were correlated with clinical parameters such as the model for end-stage liver disease (MELD) score and HE grade. Results Significant associations were found between 22 pairs of regions of interest, including the red nucleus and corpus callosum (φ = 0.81, p < 0.001), crus cerebri and red nucleus (φ = 0.72, p < 0.001), and red nucleus and dentate nucleus (φ = 0.66, p < 0.001). After hierarchical clustering, 24 cases were classified into Group I, 35 into Group II, and 39 into Group III. Group III had a higher MELD score (p = 0.04) and HE grade (p = 0.002) than Group I. Conclusion Our study demonstrates that the SRCE patterns can be useful in predicting hepatic preservation and the occurrence of cerebral failure in HE. [ABSTRACT FROM AUTHOR]

Aquaporin-4 (AQP4) is the main water channel in the central nervous system. AQP4 is highly expressed in brain structures, suggesting its crucial role in water transport in norm and in pathology. Here, we studied the effect of a change in the drinking regimen (water deprivation, hyperhydration) and inherited arterial hypertension on the expression of the AQP4 water channel gene in the hypothalamus, a regulatory brain center of visceral functions. The expression level of the Aqp4 gene in hyperhydrated animals was found to be more than 1.5 times lower than in water-deprived animals, which may reflect the need to prevent cytotoxic edema during increased fluid intake. Rats with inherited stress-induced arterial hypertension are characterized by an increased level of the Aqp4 gene in the hypothalamus, suggesting the involvement of this channel in processes associated with the regulation of brain water balance and the prevention of vasogenic cerebral edema in arterial hypertension. Thus, the presence of the AQP4 water channel in the brain, associated with the protection of brain cells, is functionally determined by the state of the body, as evidenced by bidirectional changes in Aqp4 expression during hyperhydration and arterial hypertension. [ABSTRACT FROM AUTHOR]

The mechanisms of cerebral ischemia–reperfusion injury (IRI) limitation by remote ischemic postconditioning (RPC) are of interest because the latter may positively influence functional recovery after cerebral ischemia. The study was aimed to assess the role of plasma proteins syndecan-1 (SDC-1) and annexin-5 (ANXA-5) in limiting cerebral IRI by RPC in a middle cerebral artery occlusion (MCAO) model in male Wistar rats. The animals were randomized into three groups: (1) control sham-operated rats (SO group), (2) rats with 30-min MCAO-induced ischemia (MCAO group), (3) rats with 30-min MCAO-induced ischemia followed by RPC (MCAO + RPC group). SDC-1 plasma levels, as assessed by ELISA, in MCAO (41.4 ± 1.3 ng/mL) and MCAO + RPC (67.8 ± 5.8 ng/mL) rats were, respectively, by 30% (p < 0.05) and 112% (p < 0.01) higher than in SO control (31.9 ± 1.1 ng/mL). No intergroup differences in ANXA-5 plasma levels were detected. Cerebral infarct volume in MCAO and MCAO + RPC rats accounted for 32.0 ± 2.5 and 13.6 ± 1.3% of the total brain volume, respectively (p < 0.05). Cerebral edema volume in MCAO and MCAO + RPC rats were 47.0 ± 3.3 and 16.0 ± 2.1%, respectively (p < 0.05). In MCAO + RPC animals, correlation analysis revealed a high direct correlation between infarct size and right forelimb muscular strength (grip strength test, 3.9 ± 0.8 H, p > 0.5; KK = 0.72, p < 0.05) and a very high inverse correlation between infarct size and right hindlimb capillary blood flow (Doppler flowmetry, r = –0.98, p < 0.01). Animals' neurologic deficits were assessed by the Garcia scoring scale, while their locomotor coordination was assessed in the Rotarod test. It is assumed that SDC-1 plasma protein may serve as a potential regulator of the infarct size-limiting effect of remote ischemic postconditioning, which is determinative for functional recovery. [ABSTRACT FROM AUTHOR]