Journal of Stroke and Cerebrovascular Diseases

BACKGROUNDDespite advancements in neurosurgery and intensive care that reduce overall mortality, poor-grade aneurysmal subarachnoid haemorrhage (aSAH) (World Federation of Neurosurgical Societies [WFNS] grades IV and V) remains a significant clinical challenge and is associated with persistently high mortality rates. The aim of this study was to assess the long-term outcomes of poor-grade aSAH and to identify factors influencing patient prognosis to guide clinical management. METHODSA multicentre, observational cohort study was conducted across 12 regional centres in northern China. The study included patients with poor-grade aSAH admitted from 2017 to 2020. The baseline data included demographics, clinical presentation, aneurysm characteristics, and treatment modalities. Outcome data, including survival status, mortality along with its associated causes and timing, and modified Rankin scale (mRS) scores, were collected prospectively at the last medical follow-up. Changes in case fatality over time were quantified with weighted linear regression. Survival analysis was performed to estimate survival and hazard ratios for death. Binary logistic regression was performed to estimate the odds ratio for dependency (mRS=3-5). RESULTSAmong the 1,589 enrolled patients, 1,339 were successfully followed, with an average follow-up of 26.37 months. Among them, 61.5% (824/1,339) were dependent or died. The overall mortality rate was 51% (684/1,339), and 21.3% (140/655) of the survivors were dependent. The risk factors for mortality included age [≥]65 years, previous history of stroke, and WFNS grade V. Additionally, conservative treatment and endovascular treatment were identified as risk factors and protective factors, respectively, compared with surgical treatment. WFNS grade V and middle cerebral artery aneurysms are independent risk factors for dependency. CONCLUSIONSAlthough there has been a downward trend in recent years, the long-term mortality rate for poor-grade aSAH has remained significantly high at 51%, with 21.3% of survivors being dependent. Active aneurysm treatment, to the extent possible, is crucial for improving the prognosis of these patients.

BackgroundImpairment in cerebral autoregulation has been proposed as a potentially targetable factor in patients with aneurysmal subarachnoid hemorrhage (aSAH), however there are different continuous measures that can be used to calculate the state of autoregulation. In addition, it has previously been proposed that there may be an association of impaired autoregulation with the occurrence of spreading depolarization (SD) events. MethodsSubjects with invasive multimodal monitoring and aSAH were enrolled in an observational study. Autoregulation indices were prospectively calculated from this database as a 10 second moving correlation coefficient between various cerebral blood flow (CBF) surrogates and mean arterial pressure (MAP). In subjects with subdural ECoG (electrocorticography) monitoring, SD was also scored. Associations between clinical outcomes using the mRS (modified Rankin Scale) and occurrence of either isolated or clustered SD was assessed. Results320 subjects were included, 47 of whom also had ECoG SD monitoring. As expected, baseline severity factors such as mFS and WFNS (World Federation of Neurosurgical Societies scale) were strongly associated with the clinical outcome. SD probability was related to blood pressure in a triphasic pattern with a linear increase in probability below MAP of [~]100mmHg. Autoregulation indices were available for intracranial pressure (ICP) measurements (PRx), PbtO2 from Licox (ORx), perfusion from the Bowman perfusion probe (CBFRx), and cerebral oxygen saturation measured by near infrared spectroscopy (OSRx). Only worse ORx and OSRx were associated with worse clinical outcomes. ORx and OSRx also were found to both increase in the hour prior to SD for both sporadic and clustered SD. ConclusionsImpairment in autoregulation in aSAH is associated with worse clinical outcomes and occurrence of SD when using ORx and OSRx. Impaired autoregulation precedes SD occurrence. Targeting the optimal MAP or cerebral perfusion pressure in patients with aSAH should use ORx and/or OSRx as the input function rather than intracranial pressure.

BackgroundLittle is known on the burden of ICU care for stroke patients. The aim of this study was to provide a description of management strategies, resource use, complications and their association with prognosis of stroke patients admitted to ICU. MethodsUsing a population-based stroke registry, we analyzed consecutive stroke patients admitted to 3 ICU with at least one organ failure between 2008 and 2017. The study period was divided into two periods corresponding to the arrival of mechanical reperfusion technique. Predictors of ICU mortality were separately assessed in two multivariable logistic regression models, a "clinical model" and an "intervention model". The same analysis was performed for predictors of functional status at hospital discharge. Results215 patients were included. Stroke etiology was ischemia in 109 patients (50.7%) and hemorrhage in 106 patients (49.3%). Median NIHSS score was 20.0 (9.0; 40.0). The most common reason for ICU admission was coma (41.2%) followed by acute circulatory failure (41%) and respiratory failure (27.4%). 112 patients (52%) died in the ICU and 20 patients (11.2%) had a good functional outcome (mRS[&le;]3) at hospital discharge. In the "clinical model," factors independently associated with ICU mortality were: age (OR = 1.03 [95%CI, 1.0 to 1.06]; p=0.04) and intracranial hypertension (OR = 6.89 [95%CI, 3.55 to 13.38]; p<0.0001). In the "intervention model," the need for invasive mechanical ventilation (OR = 7.39 [95%CI, 1.93 to 28.23]; p=0.004), the need for vasopressor therapy (OR = 3.36 [95%CI, 1.5 to 7.53]; p=0.003) and decision of withholding life support treatments (OR = 19.24 [95%CI, 7.6 to 48.65]; p<0.0001) were associated with bad outcome. ConclusionOur study showed the very poor prognosis of acute stroke patients admitted to ICU. These results also suggest that the clinical evolution of these patients during ICU hospitalization may provide important information for prognostication.

ObjectiveThe objective of this scoping review is to understand the extent and type of evidence in relation to the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) for neuroprotection in aneurysmal subarachnoid haemorrhage (aSAH). IntroductionThe individual and societal costs of aSAH remain high. Effective neuroprotection would reduce morbidity and mortality but there are uncertainties around both established and emerging therapies. GLP-1RA show promise as neuroprotective drugs in other forms of acute and chronic brain injury and could be repurposed for aSAH. Inclusion criteriaAnimal and human studies of the use of GLP-1RA for aSAH will be included. Key exclusions are traumatic or non-aneurysmal subarachnoid haemorrhage, or the use of multi-agonist drugs. MethodsSearches were conducted in Embase (Ovid), Medline (Ovid), Cochrane Central Register of Controlled Trials (Wiley) and the World Health Organisations International Clinical Trials Registry Platform on 13th June 2025 with no limits applied. Screening and data extraction was performed by two independent reviewers. ResultsAfter de-duplication 593 records were screened, 50 selected for full text review and 5 included in this review. GLP-1R were shown to be highly expressed in neurones and microvascular endothelial cells after aSAH. Administration of GLP-1RAs to rats affected by aSAH improved functional recovery. Furthermore, aSAH was reported to increase cerebral hemisphere oedema, blood-brain barrier permeability, cell death and inflammation, all of which were reversed by GLP-1RA treatment. Murine studies highlight potential mechanisms for these beneficial effects including inhibition of ferroptosis, downregulation of apoptosis, and upregulation of SIRT1 pathways. A human observational studies shows a correlation between higher SIRT1 levels and better neurological outcomes. ConclusionThe limited available evidence suggests a potential neuroprotective role for GLP-1RAs after aSAH. There is a need for extensive further research to determine the efficacy and safety of GLP1-RAs for neuroprotection in aSAH.

BackgroundAlthough sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association of sepsis with DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. MethodsPatients admitted to our hospital between 11/2014-11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed. ResultsOf 238 patients with aSAH, 55 (23%) developed sepsis and 74 (31%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p<0.01) and longer ICU stay (p=0.046). Sepsis was independently associated with DCI (OR=2.46, 95%CI: 1.28-4.72, p<0.01). However, after exclusion of patients who developed sepsis before (OR=1.59, 95%CI: 0.78-3.24, p=0.21) or after DCI (OR=0.85, 95%CI: 0.37-1.95, p=0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56% (76/135) in patients with neither sepsis nor DCI, to 43% (21/48) in those with no sepsis but DCI, to 34% (10/29) with sepsis but no DCI and to 8% (2/26) in patients with both sepsis and DCI. ConclusionsOur study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

BackgroundThe occurrence of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is a main determinant for functional outcome. Despite two decades of animal studies investigating novel treatment strategies, the standard therapy for delayed cerebral ischemia has not changed. This translational gap raises the question to what extent experimental mouse models of subarachnoid hemorrhage can accurately mimic human delayed cerebral ischemia. The objective of this systematic review was to determine whether there are difference in the occurrence and timing of delayed cerebral ischemia between the various experimental mouse models of aneurysmal subarachnoid hemorrhage. Our aim was to identify which mouse model most closely mimics the human pathophysiology following aneurysmal subarachnoid hemorrhage. MethodsThis study was funded by ZonMw (project number 114024130). The review was preregistered at PROSPERO (protocol ID: CRD42020115578). A comprehensive search was performed in Medline via the PubMed interface and in EMBASE via the Ovid interface up to 2nd November 2018The following exclusion criteria were used in both the title and abstract and full text phase: 1) not an original, full-length research paper, 2) no English language version available, 3) published before 1999, 4) not an animal study, 5) not a mouse study, 6) use of transgenic mice, 7) no subarachnoid hemorrhage induction, 8) no delayed cerebral ischemia measured, 9) reported an observation time less than six hours, 10) cross-over study, or any study design without a control group. Data was extracted by one reviewer. The SYRCLE risk of bias tool was used in duplo by two independent reviewers to assess risks of bias in the included studies, with discrepancies being resolved through discussion. A narrative synthesis of the evidence was performed. ResultsThe literature search retrieved a total of 1461 papers, of which 71 publications met the inclusion criteria. Most studies were assessed at an unclear risk for most types of bias. Mice models were highly standardized: the C57Bl/6 strain was used in 53 studies (74.6%), only male animals were used in 55 studies (77.5%). To model a subarachnoid hemorrhage, perforation of the anterior cerebral artery / internal carotid artery with a suture was performed in 43 studies (60.6%), while direct injection of blood was performed in 24 studies (33.8%). The presence of delayed cerebral ischemia was established through neurological outcomes (44 studies, 62.0%), ex-vivo histology (39 studies, 54.9%) or in-vivo imaging (10 studies, 14.1%) assessment. Incidence of delayed cerebral ischemia was similarly high for all outcome measures (between 85-87%) and the timing of delayed cerebral ischemia occurrence was similar, despite differences in subarachnoid hemorrhage induction method. ConclusionOur results show that established perforation and injection-models for experimental subarachnoid hemorrhage are highly standardized. Yet, there is a high inconsistency in definitions of delayed cerebral ischemia in experimental mouse models. Although perforation model results in a higher rate of delayed cerebral ischemia, there is no effect on the time of occurrence after ictus. It is unclear to what extent the delayed cerebral ischemia demonstrated in these animal models is comparable to the clinical situation.

BackgroundHemorrhage transformation (HT) after reperfusion therapy is linked with poor outcomes in acute ischemic stroke patients. This study aimed to determine the role of neuronal microRNA-383 in alleviating HT-associated injury using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation reoxygenation (OGD/R) models. MethodsIn neurons following OGD/R, the family of miR-383 and NADPH oxidase (NOX) expression was evaluated. After miR-383-5p intervention and small interfering RNA, reactive oxygen species (ROS) and neuronal injury were assessed. Two hundred and five hyperglycemic rats were used to establish the HT model induced by mechanical reperfusion after 5-hour MCAO, followed by 3 and 6 hours of reperfusion, and treated with intravenous administration of miR-383-5p agomir before reperfusion. Brain water content, hemorrhage severity, infarct volume, blood-brain barrier (BBB) disruption, neuronal apoptosis, ROS production, miR-383-5p and NOX4 expression, and BBB-associated proteins were assessed. ResultsMiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. Elevating miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression as a target of miR-383-5p, shown in OGD/R-treated neurons. In the MCAO model, increased miR-383-5p suppressed NOX4 upregulation, alleviated brain edema, infarct volume, and hemorrhage severity, reduced neuronal apoptosis and ROS overproduction, and preserved BBB integrity after mechanical reperfusion for ischemia, thereby improving short-term neurological outcomes. ConclusionsMiR-383-5p alleviates oxidative stress injury and neuronal apoptosis, and preserves BBB integrity by regulating NOX4. Neuronal miR-383-5p could become a potential target for intervention to decrease HT and ameliorate outcomes in endovascular reperfusion treatment for acute ischemic stroke.

BackgroundGuideline based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescribers blood pressure medication choice adheres to clinical practice guidelines (Prescribers-Choice Adherence). MethodsThe Florida Stroke registry (FSR) utilizes statewide data prospectively collected for all acute stroke admissions. Based on established guidelines we defined optimal Prescribers-Choice Adherence using the following hierarchy of rules: 1) use of an angiotensin inhibitor (ACEI) or angiotensin receptor blocker (ARB) as first-line antihypertensive among diabetics; 2) use of thiazide-type diuretics or calcium channel blockers (CCB) among African-American patients; 3) use of beta-adrenergic blockers (BB) among patients with compelling cardiac indication (CCI) 4) use of thiazide, ACEI/ARB or CCB class as first-line in all others; 5) BB should be avoided as first line unless CCI. RESULTSA total of 372,254 cases from January 2010 to March 2020 are in FSR with a diagnosis of acute ischemic, hemorrhagic stroke, transient ischemic attack or subarachnoid hemorrhage; 265,409 with complete data were included in the final analysis. Mean age 70 +/-14 years, 50% female, index stroke subtype of 74% acute ischemic stroke and 11% intracerebral hemorrhage. Prescribers-Choice Adherence to each specific rule ranged from 48-74% which is below quality standards of 85%. There were race-ethnic disparities with only 49% Prescribers choice Adherence for African Americans patients. ConclusionThis large dataset demonstrates consistently low rates of Prescribers-Choice Adherence over 10 years. There is an opportunity for quality improvement in hypertensive management after stroke.

BackgroundOptimal postoperative blood pressure (BP) management remains unclear for hypertensive patients with aneurysmal subarachnoid hemorrhage (aSAH). We investigated associations of early postoperative BP levels, variability, and trajectories with 6 month outcomes. MethodsConsecutive hypertensive patients after aSAH surgery were retrospectively analyzed. BP was measured four times daily for 3 days. Profiles included minimum systolic BP (SBP), mean arterial pressure, variability, and SBP trajectories. Minimum SBP was dichotomized at 140 mmHg to examine threshold effects. Multivariable logistic regression assessed associations between BP metrics and functional outcome. Causal mediation analysis evaluated the indirect effect of delayed cerebral ischemia (DCI) on the association between minimum SBP (140 mmHg cutoff) and outcome. ResultsAmong 702 patients, lower SBP in the first 3 days independently predicted poor outcomes (OR = 0.98). Maintaining SBP [&ge;]140 mmHg was linked to lower risks of unfavorable outcomes (OR = 0.44) and DCI (OR = 0.49). Mediation analysis indicated 35% of this effect was explained by reduced DCI. Higher BP variability, measured by standard deviation and coefficient of variation, correlated with poor outcomes. Trajectory analysis showed that moderately rising SBP ([&ge;]140 mmHg) was associated with the favorable outcomes. ConclusionsMaintaining SBP [&ge;]140 mmHg with stable variability in the early postoperative period was associated with favorable functional outcomes, partly through reducing DCI. These findings highlight the importance of adequately elevated and stable BP management after aSAH surgery.

The middle cerebral artery occlusion (MCAO) suture model is widely accepted ischemic stroke model. However, researchers routinely use young male rats, ignoring that stroke risk is increased in older, post-menopausal women. To this end, we implemented (120-minute) transient- and permanent-occlusion MCAO models in female retired-breeder rats, examining the endpoint across 1-30 days to identify the optimal time course for the model. We found that in both groups the physical infarct (measured by triphenyltetrazolium chloride -TTC staining), which is present initially, was not detectable 30 days post-MCAO (even if some neurologic symptoms persist). Across shorter time-points (namely 24 hours and 7 days) we found that neurologic scores generally reach a plateau/maximum at {bsim}7 days, then infarct size gradually decreases over time for rats receiving a permanent MCAO. Across 3 transient occlusion times (60 minutes, 90 minutes, and 120 minutes), the longest gave the most robust result. Overall, the permeant and 120-minute transient MCAO evaluated at 7 days was optimal. Using these two models, we evaluated the neuroprotective qualities of the antibiotic, minocycline. We found that those in the treatment groups experienced a greater improvement in neurologic scores and a larger decrease in infarct size after daily treatment for seven days. This improvement was more prominent in the transiently occluded treatment group than in the permanently occluded group.

Ischaemic stroke treatment is limited to recanalizing the occluded vessel, while there is no approved adjunctive cerebroprotective therapy to protect either the neurons and parenchyma or the neurovascular unit. Pharmacological inhibition of mammalian target of rapamycin-1 (mTORC1) with rapamycin has shown promise in reducing infarct volume and improving functional outcomes. However, previous studies that investigated the effects of rapamycin on the vasculature and cerebral blood flow (CBF), administered rapamycin prior to or during stroke induction, thus limiting the potential for clinical translation. Therefore we investigated whether rapamycin maintains its cerebrovascular protective effect when administered immediately after recanalization following 90 minutes stroke in Wistar rats. We show, that rapamycin significantly improved post-recanalization cerebral blood flow (CBF), suggesting a beneficial neurovascular effect of rapamycin. Rats treated with rapamycin had smaller infarct volumes and improved functional outcomes compared to the control animals at three days post-stroke. The mechanisms of the overall positive effects seen in this study are likely due to rapamycins hyperacute effects on the neurovasculature, as shown with increased CBF during this phase. This paper shows that rapamycin treatment is a promising adjunct cerebroprotective therapy option for ischemic stroke.

IntroductionCurrent reports indicate that the increased use of social distancing for preventive COID-19 distribution may have a negative effect on patients who suffering from acute medical conditions. AimWe examined the effect of social distancing on acute ischemic stroke (AIS) patients referral to the emergency department (ED) MethodA retrospective archive study was conducted between January 2017 and April 2020 in a comprehensive stroke center. We compare the number of neurologic consultations, time from symptoms onset to ED arrival, patients diagnosis with AIS, number of patients receiving treatment (tPA, endovascular thrombectomy (EVT) or combine) and in-hospital death. ResultsThe analysis included a total of 14,626 neurological consultations from the years 2017 to 2020. A significant decrease of 58.6% was noted during the months of January-April of the year 2020 compared to the parallel period of 2017. Percent of final AIS diagnosis for the year of 2020 represent 24.8% of suspected cases, with the highest diagnosis rate demarcated for the year of 2019 with 25.6% of confirmed patients. The most remarkable increase was noted in EVT performance through the examined years (2017, n=21; 2018, n=32; 2019, n=42; 2020, n=47). ConclusionCOVID-19 pandemic resulted in routing constraints on health care system resources that were dedicated for treating COVID-19 patients. The healthcare system must develop and offer complementary solutions that will enable access to health services even during these difficult times.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke associated with higher morbidity and mortality. Posterior circulation aneurysms are considered to have worse prognosis than anterior circulation aneurysms due to anatomical location, hemorrhage severity, and treatment complexity. We aimed to determine whether aneurysm location independently influences clinical outcomes following aSAH Methods: PubMed, Scopus, Embase, and Web of Science were searched from January 2000 to December 2025 for studies reporting outcomes in anterior or posterior circulation aSAH. The outcome analysis included mortality, functional recovery (modified Rankin Scale [mRS] 0-2 and 3-6 at 6 months and 1 year), hydrocephalus, delayed cerebral ischemia (DCI), and symptomatic cerebral vasospasm. Pooled proportions and subgroup comparisons were performed using random-effects meta-analysis (DerSimonian-Laird method). Publication bias was evaluated using contour-enhanced funnel plots and Egger's test. Results: Nineteen analytic entries from 18 studies (anterior: n = 1,625; posterior: n = 986; total N = 2,611) were included. Pooled mortality was 13% (95% CI: 10%-17%; I2 = 84.6%), with no significant difference between the anterior (14%; 95% CI: 10%-20%) and posterior (11%; 95% CI: 7%-18%) circulation subgroups (p = 0.437). Good functional outcome was 60% at 6 months (95% CI: 51%-67%) and 55% at 1 year (95% CI: 46%-64%), with no location-based differences. Hydrocephalus (35% vs 35%; p = 0.979) and DCI (17% vs 17%; p = 0.939) were comparable between subgroups. Symptomatic cerebral vasospasm was the only outcome differing significantly by location, occurring more frequently in anterior circulation aSAH (24% vs 11%; {chi}2 = 5.59; p = 0.018). Conclusion: Aneurysm location does not independently determine mortality, functional recovery, hydrocephalus, or DCI following aSAH. Symptomatic cerebral vasospasm was the only location-specific outcome. Admission neurological grade (World Federation of Neurosurgical Societies [WFNS]), rather than vascular territory, appears to be the primary determinant of mortality. Aneurysm location alone should not guide prognostic decisions or limit aggressive treatment.

IntroductionIntracranial aneurysm (ICA) rupture is the most common cause of non-traumatic subarachnoid hemorrhage, a devastating type of stroke. Vascular smooth muscle (VSMC) and endothelial cell (EC) dysfunction and death play important roles in the etiology of ICA formation, rupture and treatment failure. Mesenchymal stem cells (MSCs) have been extensively investigated for their therapeutic potential in vascular diseases. The mammalian target of rapamycin (mTOR) is a key regulatory pathway involved in cellular functions controlling intracellular anabolic and regulatory processes. Rapamycin, a specific mTOR complex 1 inhibitor, is widely used in the clinical management of cardiac and vascular pathologies. In this study, we explored MSCs potential to express VSMC and EC markers under the influence of rapamycin. MethodsHuman MSCs were treated with rapamycin for 2, 5, and 10 days, and cell death and proliferation determined by MTT analysis. Protein expression and phosphorylation levels were determined by western blot analysis. Calcein AM and PI staining was used to determine cell viability, and morphology. ResultsMTT and Calcein AM analysis demonstrated that prolonged rapamycin treatment did not affect MSC viability but was found to reduce MSC proliferation and cause a nearly threefold increase in cell size compared to controls. Rapamycin treatment increased expression of the VSMC protein markers, -SMA, and transgelin and was required to maintain elevated expression levels both proteins. In contrast, selective inhibition of mTORC2 with JR-AB2-01 caused a decrease in -SMA and trangelin expression, suggesting mTORC1 regulation of -SMA and transgelin expression, rather than mTORC2. Rapamycin treated MSC were also found to induce cell sprouting between adjacent cells. MSCs were found not to express endothelial protein markers under either basal conditions or following rapamycin treatment. However, rapamycin treatment was found to increase VEGFA expression, a known promoter of angiogenesis. ConclusionRapamycin has the potential to increase VSMC protein expression in MSCs by its action on mTORC1. The ability of rapamycin to increase VEGFA expression in MSCs could allow for a novel MSC-based therapeutic intervention in cerebral aneurysm management which could aid in ICA healing and reducing rupture risk.

BackgroundInflammation has been found to be largely detrimental early in the acute phase of stroke but beneficial at more chronic stages. Fasting has been shown to reduce inflammation acutely. We aimed to determine whether post-ischemic fasting improves stroke outcomes through attenuated inflammation. MethodsAfter an endothelin-1 lesion was created in the striatum, animals were subjected to either normal feeding or water-only fasting for 24 hours. ResultsIt was found that at 24 hours, fasting reduced infarct volume and BBB breakdown and lowered both circulating and brain neutrophils. ConclusionsThese findings suggest that fasting is a potentially beneficial non-pharmacological additive therapeutic option for cerebral ischemia, which might act by reducing inflammation in the acute disease stage.

BackgroundDelayed cerebral ischemia (DCI) due to vasospasm following subarachnoid hemorrhage (SAH) is considered a significant determinant of morbidity and mortality; however, no established method exists to prevent and treat vasospasm or DCI. This study aimed to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and DCI. MethodsWe retrospectively identified 340 SAH patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. Ventricular/cisternal drainage (VD/CD) was inducted during aneurysm surgery, and lactated Ringers solution was used for irrigation until day 4 of SAH, followed by ICP control at 5-10 cmH2O until day 14. We collected data on total vasospasm, DCI, and modified Rankin Scale scores at discharge and analyzed the risk factors using logistic regression models. ResultsThe median age was 65 years (interquartile range: 52-75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: Grade I or II, 175 cases (51%); Grade III or IV, 84 (25%); Grade V, 81 (24%). With VCI management in all cases, total vasospasm occurred in 162 patients (48%), but DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventivefactor against DCI occurrence (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.07-0.67; p = 0.008), while additional surgery (OR 4.76, 95% CI 1.62-13.98; p = 0.005) and dyslipidemia (OR 3.27, 95% CI 1.24-8.63; p = 0.017) were associated with DCI occurrence. ConclusionsManaging vasospasms with VCI after SAH achieved a low incidence of 6.8% for DCI and is considered a safe and effective method. Early surgery after SAH occurrence was associated with a decreased risk of DCI with VCI therapy.

Background and PurposeNo effective treatment is available for most patients who suffer ischemic stroke. Development of novel treatment options is imperative. The brain attempts to self-heal after ischemic stroke via various mechanism mediated by restored blood circulation in affected region of brain but this process is limited by inadequate angiogenesis or neoangiogenesis. Encephalomyosynangiosis (EMS) is a neurosurgical procedure that achieves angiogenesis with low morbidity in patients with moyamoya disease, reducing risk of stroke. However, EMS, surgery has never been studied as an therapeutic option after ischemic stroke. Here we described a novel procedure and feasibility data for EMS after ischemic stroke in mice. MethodsA 60 mins of middle cerebral artery occlusion (MCAo) was used to induce ischemic stroke in mice. After 3-4 hours of MCAo onset/sham, EMS was performed. Mortality of EMS, MCAo and. MCAo+EMS mice was recorded up to 21 days after surgery. Graft tissue viability was measured using a nicotinamide adenine dinucleotide reduced tetrazolium reductase assay. ResultsEMS surgery after ischemic stroke does not increase mortality compared to stroke alone. Graft muscle tissue remained viable 21 days after surgery. ConclusionsThis novel protocol is effective and well-tolerated, may serve as novel platform for new angiogenesis and thus recovery after ischemic stroke. If successful in mice, EMS can a very feasible and novel treatment option for ischemic stroke in humans.

ObjectiveThe objective of this scoping review is to understand the extent and type of evidence in relation to the use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for neuroprotection in aneurysmal subarachnoid haemorrhage (aSAH). IntroductionThe individual and societal costs of aSAH remain high. Effective neuroprotection would reduce morbidity and mortality but there are uncertainties around both established and emerging therapies. GLP1-RA show promise as neuroprotective drugs in other forms of acute and chronic brain injury and could be repurposed for aSAH. Inclusion criteriaAnimal and human studies of the use of GLP1-RA for aSAH will be included. Key exclusions are traumatic or non-aneurysmal subarachnoid haemorrhage, or the use of multi-agonist drugs. MethodsSearches will conducted in Embase (Ovid), Medline (Ovid), Cochrane Central Register of Controlled Trials (Wiley) and the World Health Organisations International Clinical Trials Registry Platform with no limits applied. Studies for data extraction will be identified by two independent reviewers after screening of titles and abstracts then full text review of potentially relevant articles against inclusion criteria. Data will be extracted by two independent reviewers using a charting tool based on the Joanna Briggs Institute template. A narrative review and summary of findings will be presented.

BackgroundWhile left ventricular (LV) venting reduces LV distension in cardiogenic shock patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO), it may also amplify risk of acute brain injury (ABI). We investigated the hypothesis that LV venting is associated with increased risk of ABI. We also compared ABI risk of the two most common LV venting strategies, percutaneous microaxial flow pump (mAFP) and intra-aortic balloon pump (IABP). MethodsThe Extracorporeal Life Support Organization registry was queried for patients on peripheral VA-ECMO for cardiogenic shock (2013-2024). ABI was defined as hypoxic-ischemic brain injury, ischemic stroke, or intracranial hemorrhage. Secondary outcome was hospital mortality. We compared no LV venting with 1) LV venting, 2) mAFP, and 3) IABP using multivariable logistic regression. To compare ABI risk of mAFP vs. IABP, propensity score matching was performed. ResultsOf 13,276 patients (median age=58.2, 69.9% male), 1,456 (11.0%) received LV venting (65.5% mAFP and 29.9% IABP), and 525 (4.0%) had ABI. After multivariable regression, LV-vented patients had increased odds of ABI (adjusted odds ratio (aOR)=1.76, 95% CI=1.29, 2.37, p<0.001) but no difference in mortality (aOR=1.08, 95% CI=0.91-1.28, p=0.39) compared to non-LV-vented patients. In the propensity- matched cohort of IABP (n=231) vs. mAFP (n=231) patients, there was no significant difference in odds of ABI (aOR=1.35, 95%CI=0.69-2.71, p=0.39) or mortality (aOR=0.88, 95%CI=0.58-1.31, p=0.52). ConclusionsLV venting was associated with increased odds of ABI but not mortality in patients receiving peripheral VA-ECMO for cardiogenic shock. There was no difference in odds of ABI or mortality for IABP vs. mAFP patients. Clinical PerspectiveIn patients receiving peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock, left ventricular venting is associated with increased odds of acute brain injury (ABI) but not mortality. However, mode of venting--intra-aortic balloon pump (IABP) or percutaneous microaxial flow pump (mAFP)--does not appear to impact either odds of ABI or mortality. These findings highlight a link between venting strategies and neurological outcomes in this high-risk population. Clinicians must weigh the benefits of venting against ABI risk when managing neurocritically ill patients, though our findings provide reassurance clinicians that both IABP and mAFP may offer comparable neurologic safety profiles.

Sphingosine-1-phosphate receptor 1 (S1PR1) is highly expressed in endothelial cells and receptor activation plays an important role in mediating endothelial function and health, thus showing promise as a pharmacologic target for acute ischemic stroke (AIS) treatment. Here, we examined the effect of a selective S1PR1 ligand, RP101075, on infarct volume and neurological outcome in adult male mice subjected to transient middle cerebral artery occlusion (tMCAO). Concomitantly, we examined S1PR1 expression profile in the ischemic mouse brain, as well as S1PR1 expression and impact of receptor activation on human brain microvascular endothelial cell (HBMEC) proliferation and survival following hypoxia plus glucose deprivation (HGD). We observed that RP101075 administration at onset of reperfusion reduced infarct volume and lessened neurological deficits in tMCAO mice and these responses were S1PR1 dependent. Additionally, we observed that tMCAO increased brain S1PR1 protein levels and flow cytometry revealed increases in S1PR1 levels are greatest in brain endothelial cells compared to other brain cell types (astrocyte, neuron, microglia). In cultured HBMECs, RP101075 increased cell proliferation and ozanimod, parent compound of RP1010175, increased live cell count during HGD; this response was S1PR1 dependent. In conclusion, S1PR1 activation improves neuroprotection/outcome post-stroke and preserves brain endothelial cell survival following ischemia-like injury.