Translational Insights Into Pericyte-Mediated Regulation of Cerebral Blood Flow: Implications for Ischemic Stroke

Stroke, Ahead of Print. Microvascular reperfusion stands as a critical therapeutic objective in ischemic stroke management. Pericytes, specialized contractile mural cells enveloping cerebral capillaries, serve as master regulators of capillary tone and regional hemodynamics, exerting a profound influence on post-ischemic stroke blood flow dynamics. Despite their pivotal role in microcirculatory control, there are limited therapeutic targets specifically aimed at regulating their activity. Here, we summarize the multifaceted roles of pericytes in ischemic stroke and discuss various pericyte-related strategies for ischemic stroke. While these interventions offer some benefits, they also present notable limitations, including adverse reactions, structural instability, suboptimal efficacy, and challenges in clinical translation. Future efforts directed toward deciphering the spatiotemporal responses of pericytes across different ischemic phases and achieving their selective and effective regulation are expected to yield novel strategies for precision microcirculatory rehabilitation.

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Hypodensity Beyond the Ischemic Core: Penumbral Changes Detected With Relative Noncontrast Computed Tomography

Stroke, Ahead of Print. BACKGROUND:In acute ischemic stroke, infarcted tissue gradually becomes detectable on noncontrast computed tomography (NCCT) as a hypodensity representing vasogenic edema. We studied whether subtle NCCT density changes are also present in penumbral tissue.METHODS:This observational cohort study included patients with stroke with anterior circulation occlusions from the CRISP2 study (CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project 2) who were transferred from a primary to a comprehensive stroke center for consideration of endovascular thrombectomy. Patients received baseline NCCT and computed tomography perfusion at the referring hospital and magnetic resonance imaging at the receiving hospital. We created baseline relative NCCT images, which compare voxel density to the corresponding area in the contralateral hemisphere. We analyzed the relative density of rNCCT in the core and penumbra (based on computed tomography perfusion in referring hospitals). We also assessed the correlation between relative density and the degree of hypoperfusion in the penumbra, defined as the time-to-maximum of the tissue residue function. We studied the association between penumbral changes and functional outcomes on the full distribution of the modified Rankin Scale score at 90 days.RESULTS:From the 314 patients, 162 met inclusion criteria with a median (interquartile range) age of 73 (61–83) years, penumbra volume of 78 (52–113) mL, and core volume of 0.6 (0–13.0) mL; 54% were men. The relative density was reduced by a median of 1.8% (P

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Blood-Brain Barrier Disruption Predicts Poor Outcome in Subarachnoid Hemorrhage: A Dynamic Contrast–Enhanced MRI Study

Stroke, Ahead of Print. BACKGROUND:Spontaneous aneurysmal subarachnoid hemorrhage induces early blood-brain barrier permeability dysfunction, although its clinical relevance and underlying mechanisms remain poorly understood. We aimed to evaluate the association between blood-brain barrier disruption, quantified with dynamic contrast–enhanced magnetic resonance imaging at the end of the early brain injury period, circulating neuroinflammatory mediators, and long-term clinical outcomes.METHODS:We analyzed a prospective cohort of subarachnoid hemorrhage patients who underwent dynamic contrast–enhanced magnetic resonance imaging at a median (interquartile range) of 4 (2–6) days after clinical onset. Permeability maps were used to obtain K-trans values as a measure of increased blood-brain barrier permeability in the whole brain, gray matter, and white matter. Circulating neuroinflammatory molecules, including IL (interleukin) 8 and PDGF (platelet-derived growth factor), were measured using Multiplex-ELISA in blood samples collected concurrently with magnetic resonance imaging acquisition. Poor clinical outcome was defined as a modified Rankin Scale score of >2 at 90 days. Associations between K-trans values, neuroinflammatory mediators, and clinical outcomes were assessed using univariate and multivariate regression models.RESULTS:From 153 patients initially screened, 96 were finally included (63% females; median age, 55 years; 43% premorbid hypertension; 32% World Federation of Neurosurgical Societies grade 4–5; 31% poor outcome). In adjusted linear regression analyses, higher K-trans values were significantly associated with increased IL-8 (P=0.001) and PDGF (P=0.018) levels. In univariate analysis, K-trans values in white matter were significantly higher in patients with poor clinical outcome (median [interquartile range], 2.5 [2.07–6.09] ×10−3·min−1) compared with good clinical outcome (median [interquartile range], 2.0 [1.60–2.42] ×10−3·min−1;P

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Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection

Stroke, Ahead of Print. Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS’s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.

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Thrombectomy Versus Medical Management for Pediatric Arterial Ischemic Stroke With Large Baseline Infarct

Stroke, Ahead of Print. BACKGROUND:Multiple recent randomized trials have demonstrated the benefit of thrombectomy over medical management alone in adult patients with large vessel occlusion (LVO) stroke and large infarct on baseline imaging. Cohort studies have also identified improved functional outcomes in pediatric patients who received thrombectomy. However, the role of thrombectomy in pediatric stroke with large baseline infarct remains uncertain.METHODS:A case-control study was undertaken using pooled data from 3 cohort studies of pediatric stroke (Save ChildS, Save ChildS Pro, Pediatric LVO Stroke Study). Pediatric patients of age 1 to 18 years with acute anterior circulation LVO stroke presenting within 24 hours since last seen well with an Alberta Stroke Program Early Computed Tomography (CT) Score of 0 to 5 on CT or magnetic resonance imaging were included. Isolated M2 occlusion or focal cerebral arteriopathy–inflammatory subtype cases were excluded. Thrombectomy-treated patients were compared with patients who received medical management alone. The primary clinical outcome was the pediatric modified Rankin Scale score at 90 days, compared between groups using ordinal logistic regression.RESULTS:Of 56 pediatric patients with anterior circulation LVO and low Alberta Stroke Program Early CT Score presenting between January 1, 2000 and August 31, 2023 from 45 centers across Europe, North America, and Australia, 40 patients were eligible for inclusion (female: n=14, 35.0%; mean age, 9.1 years; range, 1.5–17; SD, 5.27). Thrombectomy-treated patients (n=24) had significantly better pediatric modified Rankin Scale scores at 90 days than medical management alone patients (n=16; odds ratio, 3.68 [95% CI, 1.11–12.21];P=0.034). There was no significant difference between groups in the rate of symptomatic intracranial hemorrhage (P=0.806).CONCLUSIONS:In this multicentre case-control study, pediatric patients (age, 1–18 years) with anterior circulation LVO stroke and low Alberta Stroke Program Early CT Score who received thrombectomy had significantly better functional outcomes than those treated with medical management alone. Exclusion of pediatric patients from thrombectomy based on low Alberta Stroke Program Early CT Score alone may not be appropriate.

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Prognostic nutritional index in the prediction of adverse cardiac and cerebrovascular events in ST-segment elevation myocardial infarction patients with type 2 diabetes mellitus in Urumqi, China: a retrospective cohort study

Objective
Prognostic nutritional index (PNI) is an index for assessing nutritional and immune status. The aim of this study is to investigate the predictive value of PNI for long-term major adverse cardiac and cerebrovascular events (MACCE) in ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (T2DM).

Design, setting and participants
This retrospective cohort study analysed 1582 STEMI patients with T2DM who underwent percutaneous coronary intervention from January 2015 to June 2023 in Urumqi, China. Patients were followed up for MACCE.

Primary and secondary outcome measures
The primary endpoint was new-onset MACCE including all-cause death, non-fatal MI and non-fatal stroke.

Results
This study ultimately included 1582 patients for analysis with a median follow-up period of 48 months (IQR: 24–84 months) and 282 patients (17.8%) developed MACCE. Of them, 138 (8.7%), 84 (5.3%) and 60 (3.8%) patients developed all-cause death, a non-fatal MI and a non-fatal stroke, respectively. Incidences of MACCE and all-cause death conversely correlated with PNI. Kaplan-Meier curves showed a significant difference in all components of MACCE between PNI quartiles (p

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Understanding disparities in access to and quality of surgical care for African, Caribbean and Black communities in high-income countries with universal healthcare: a scoping review protocol

Introduction
African, Caribbean and Black (ACB) communities experience disparities in health outcomes, with higher rates of chronic diseases, such as heart disease and stroke, and lower self-reported health status compared to their White counterparts. Barriers to timely access to healthcare services further exacerbate these inequities. Some studies link racialisation to surgical disparities and subpar surgical outcomes. However, the findings are diverse, and there is no synthesis of the evidence on disparities in surgical care for ACB patients in high-income countries with universal healthcare systems. The objective of the scoping review is to systematically describe, characterise and map the existing literature on disparities in the access to and quality of surgical care among ACB patients in high-income countries with universal healthcare systems, and to identify gaps in the literature on surgical access and quality of surgical care in ACB patients.

Methods and analysis
The scoping review will follow the Joanna Briggs Institute methodology and report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The search strategy will be customised for each database (MEDLINE, Embase, CINAHL, APA PsycINFO and Cochrane Library) using terms for ACB and surgery. Grey literature and references from included studies will be searched for additional sources, with no limitations on publication date or language. All study designs will be eligible. Two independent reviewers will screen titles, abstracts and full texts in duplicate for eligibility. One reviewer will chart data, with a second reviewer validating the data charted. The findings will be synthesised, quantitatively summarised using descriptive statistics and qualitatively analysed through thematic analysis.

Ethics and dissemination
Ethics approval is not required as the study utilises published data. The dissemination of the findings will inform future research and improve understanding of the surgical care experiences of ACB patients. Dissemination will target academics and healthcare professionals through publications, presentations and workshops.

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Fifty Years of Deciphering Stroke Pathophysiology

Stroke, Volume 56, Issue 7, Page 1947-1957, July 1, 2025. In the 2025 David G. Sherman Lecture, Jean-Claude Baron emphasizes the major role positron emission tomography played in the breakthroughs in ischemic stroke pathophysiology that took place in the last half-century and allowed major therapeutic advances. Based on his work using PET in both animal models and people with stroke spanning 4 decades, he details his main contributions to key milestones, including (1) the demonstration of the hemodynamic consequences of chronic carotid artery occlusion and the hemodynamic mechanism underlying some transient ischemic attacks; (2) the documentation of the existence of the ischemic penumbra in man and the formal validation, using stringent prespecified operational criteria, of the core/penumbra model; (3) the persistence of substantial penumbral volumes up to 17 hours after stroke onset in a substantial fraction of patients; (4) the demonstration that from early timepoints poststroke, a good fraction of patients do not show the extensive penumbral pattern but instead exhibit large cores or spontaneously reperfusion, indicating the importance of individual patient selection for trials and therapy based on physiological imaging instead of time since stroke onset; (5) the documentation that the salvaged penumbra may not be intact but is often affected by selective neuronal loss, which may impact functional outcome and represent a novel target for neuroprotection; and (6) the demonstration of remote metabolic effects of disconnection resulting in loss of excitatory input, such as crossed cerebellar diaschisis and thalamocortical diaschisis, which may represent additional targets for therapies aiming at adaptive plasticity.

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COSMOS: Interrater and Intrarater Reliability Study of a Novel Outcome Measure

Stroke, Volume 56, Issue 7, Page 1958-1964, July 1, 2025. The vast majority of patients with minor stroke achieve what are considered good or excellent outcomes on the modified Rankin Scale (0–1/0–2), yet many are dissatisfied with their outcomes. There is a need for a functional outcome measure tailored for minor stroke that better reflects the spectrum of clinical outcomes within this population. We developed the Canadian Outcome Scale for Minor Stroke (COSMOS) and performed an interrater and intrarater reliability study. COSMOS is a 7-point scale ranging from 0 (no symptoms) to 6 (loss of independence for an instrumental or basic activity of daily living or worse), which accounts for performance limitations and losses of a person’s hobbies or passions and of their employment, educational, service, or caregiving pursuits, besides just activities of daily living. One hundred test case vignettes were developed. Stroke physicians, fellows, and research nurses/staff were invited to review training materials and provide the COSMOS grade for 20 cases representing all COSMOS grades (0–6). After a minimum 2 weeks’ wash-out period, participants were asked to grade the same 20 cases again. Interrater and intrarater agreement were assessed using Cohen κ, weighted κ, percentage agreement, and intraclass correlation coefficient. Among 33 participants (18 attending physicians, 9 stroke fellows, and 6 research staff/nurses; median 12.5 years of experience), COSMOS had substantial interrater reliability (80.5% agreement [95% CI, 75.7%–85.3%]; Cohen κ, 0.77 [95% CI, 0.72–0.84]) and almost-perfect intrarater reliability overall (87.1% agreement [95% CI, 84.4%–89.7%]; Cohen κ, 0.85 [95% CI, 0.82–0.88]); weighted κ showed almost perfect agreement for both interrater (0.88 [95% CI, 0.85–0.92]) and intrarater reliability (0.92 [95% CI, 0.90–0.94]). The overall chance-adjusted simultaneous intrarater/interrater agreement using intraclass correlation coefficient was 0.95 (95% CI, 0.94–0.97). Results were similar with substantial to almost-perfect agreement when considering key subgroups based on position (attendings, fellows, research nurses/staff) and years of experience. In conclusion, the newly proposed COSMOS scale demonstrated substantial interrater and intrarater reliability. The scale merits further study in cohort studies and clinical trials of minor stroke.

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