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        <title>Frontiers in Neurology | Stroke section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/neurology/sections/stroke</link>
        <description>RSS Feed for Stroke section in the Frontiers in Neurology journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-08-23T00:42:36.849+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1881451</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1881451</link>
        <title><![CDATA[A Bayesian conditional probability simulation framework for pre-hospital stroke transport decisions in the tenecteplase era: decision boundaries, global sensitivity, and stochastic dominance]]></title>
        <pubdate>2026-08-21T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Tuǧba Çalışır</author>
        <description><![CDATA[Acute ischaemic stroke triage between Drip-and-Ship (DS), Mothership (MS) and Mobile Stroke Unit (MSU) strategies has been formalised over the past decade by conditional-probability decision models. Two recent developments motivate an updated treatment: the shift of the intravenous thrombolysis standard from alteplase to tenecteplase, and the maturation of randomised evidence on DS-versus-MS triage and on MSU effectiveness. A Bayesian conditional-probability simulation framework is presented that combines random-effects synthesis of the modern trial corpus for intravenous thrombolysis (alteplase, tenecteplase) and endovascular thrombectomy with a log-normal decomposition of onset-to-reperfusion into strategy- and pharmacology-specific process-time components. The prehospital large-vessel-occlusion probability is updated from validated screening scales, and the optimal strategy together with a 95% posterior credible interval is computed at every coordinate of the decision space spanned by the inter-facility transit-time differential and the LVO posterior probability. Sobol first-order and total-effect indices decompose outcome variance over the sampled input space, and first- and second-order stochastic dominance between strategies is tested under the same posterior. Under the production calibration the tenecteplase paradigm reallocated 14.1% of the decision plane relative to alteplase, concentrated in the low-probability, long-differential region; the prehospital large-vessel-occlusion posterior accounted for the dominant share of outcome variance (Sobol first-order index 0.84–0.93); and no coordinate of the decision plane reached 95% posterior agreement on a single optimal strategy. The framework is open and reproducible and depends only on published trial-level evidence. It is presented as a decision-analytic and hypothesis-generating tool for structuring the tenecteplase-era triage question rather than as a validated operational triage rule, and prospective calibration against region-specific stroke-system data would be required before any deployment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1808012</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1808012</link>
        <title><![CDATA[Treatment time metrics and functional outcomes after endovascular thrombectomy in routine clinical practice]]></title>
        <pubdate>2026-08-21T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yu Qiao</author><author>Yan Yan</author><author>Tengfei Guo</author><author>Liyun Wang</author><author>Lin Wang</author>
        <description><![CDATA[BackgroundRandomised clinical trials have shown that functional outcomes after acute ischaemic stroke decline with each hour of delay to endovascular treatment. However, these estimates may not fully reflect real world practice because trial populations are highly selected and workflow conditions differ from routine care. We therefore examined the associations of prehospital and in-hospital treatment times with functional outcomes and safety endpoints among patients undergoing endovascular thrombectomyat a large comprehensive stroke centre.MethodsWe conducted a study of consecutive patients with large vessel occlusion treated with endovascular therapy between 2024 and 2025. The primary outcome was the modified Rankin Scale at 90 days, analysed using ordinal logistic regression. Secondary outcomes included excellent, independent, and favourable recovery, mortality, successful reperfusion, and symptomatic intracranial haemorrhage. Models were adjusted for demographic factors, prestroke functional status, baseline stroke severity, infarct burden, and occlusion characteristics.ResultsAmong 288 patients, longer onset-to-puncture time was independently associated with worse functional outcome. Compared with treatment achieved within less than 4.5 h, onset-to-puncture intervals of 4.5 to 6 h and greater than 6 h were associated with higher odds of poorer modified Rankin Scale outcomes. Delays beyond 6 h were also associated with increased 90-day mortality. No significant associations were observed between treatment timing and successful reperfusion or symptomatic intracranial haemorrhage.ConclusionIn routine clinical practice, shorter onset-to-puncture times are associated with more favorable functional outcomes after endovascular thrombectomy, whereas treatment beyond 6 h is associated with higher mortality. These findings highlight the importance of minimizing avoidable delays in acute stroke care while underscoring the need to interpret time-based metrics within the context of patient selection and stroke heterogeneity.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1884021</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1884021</link>
        <title><![CDATA[Safety and efficacy of idarucizumab-assisted thrombolysis in dabigatran-related acute ischemic stroke: a systematic review and single-arm meta-analysis]]></title>
        <pubdate>2026-08-20T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>Xiaoyuan Guo</author><author>Hang Xiong</author><author>Wenping Li</author><author>Qian Liu</author><author>Wei Li</author><author>Lingbo Kong</author><author>Xinxing Lai</author>
        <description><![CDATA[BackgroundIntravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) related to dabigatran use requires prior anticoagulation reversal. This study aimed to evaluate the safety and efficacy of IVT following idarucizumab-mediated reversal through a systematic single-arm meta-analysis.MethodsWe systematically searched multiple databases. Single-arm studies (≥5 patients) on idarucizumab-facilitated IVT for dabigatran-related AIS were included. Outcome data from DOAC patients without reversal in the Meinel 2023 cohort (n = 580) served as a descriptive external reference. Pooled proportions for safety (symptomatic intracranial hemorrhage, sICH) and efficacy (90-day good functional outcome, mRS 0–2) were calculated using a random-effects GLMM.ResultsEleven single-arm studies (226 patients) were included. The pooled sICH rate was 5.4% (95% CI 2.6–10.6%; τ2 = 0.362, Q p = 0.12). The pooled 90-day good functional outcome rate was 66.6% (95% CI 54.2–77.1%; τ2 = 0.116). In the external reference cohort, the sICH rate was 3.1% and the good outcome rate was 42.4%. Due to baseline imbalances and lack of confounder adjustment, descriptive comparisons were hypothesis-generating only. The certainty of evidence was rated very low (GRADE).ConclusionCurrent evidence is insufficient to guide routine clinical practice. However, these findings provide useful effect-size estimates (sICH ~5%, good outcome ~67%) for designing future randomised controlled trials. Multicenter prospective registries or pragmatic RCTs are warranted.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1903189</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1903189</link>
        <title><![CDATA[Dynamic trajectories of inflammatory biomarkers and post-stroke cognitive impairment: a comprehensive review of neuroimmune mechanisms, longitudinal modeling, and clinical translation]]></title>
        <pubdate>2026-08-20T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Hongyu Hao</author><author>Hongmin Ding</author><author>Jiayu Zhang</author><author>Peiyuan Lv</author>
        <description><![CDATA[Post-stroke cognitive impairment (PSCI) affects 30–50% of acute ischemic stroke survivors within the first year, yet the prognostic relevance of dynamic inflammatory trajectories remains incompletely defined. This narrative review synthesizes clinical and mechanistic evidence linking temporally evolving inflammatory biomarkers to vascular cognitive impairment after acute ischemic stroke. A structured evidence search of PubMed, MEDLINE, Embase, and Google Scholar from database inception to June 2026 prioritized longitudinal inflammatory-biomarker cohorts, trajectory-modeling analyses, machine-learning prediction studies, and mechanistic literature on neuroimmune injury. The available evidence indicates that post-stroke inflammation follows a multiphasic course, including hyperacute activation, acute peaking, subacute resolution, and, in a subset of patients, persistent low-grade inflammation. Delayed resolution or persistent elevation of interleukin-6, C-reactive protein, and the neutrophil-to-lymphocyte ratio appears to predict PSCI more accurately than single admission measurements. Mechanistically, sustained inflammatory signaling may contribute to chronic microglial activation, mCRP/VE-cadherin-mediated blood–brain barrier disruption, hippocampal and Papez-circuit vulnerability, and secondary neurodegeneration. Trajectory-based modeling, including latent class approaches and machine learning, may therefore improve PSCI risk stratification and support personalized follow-up and anti-inflammatory prevention trials. Larger prospective cohorts with standardized sampling and cognitive assessment are required to validate these translational applications.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1900039</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1900039</link>
        <title><![CDATA[Evidence for a dose–response association of hyperuricemia with stroke incidence: a meta-analysis of cohort studies]]></title>
        <pubdate>2026-08-19T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>Yuening Liu</author><author>Jie Wang</author><author>SaiWei Bai</author><author>Hong Ji</author>
        <description><![CDATA[BackgroundUric acid is considered a potential risk factor for stroke; However, whether the association between hyperuricemia and stroke outcomes follows a linear or nonlinear pattern remains unclear. Therefore, this study conducted a dose–response meta-analysis based on cohort studies to investigate the association between hyperuricemia and stroke outcomes.MethodsWe systematically searched PubMed, the Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and the Chinese Biomedical Literature Database from inception to April 2026. Cohort studies reporting the associations of uric acid with stroke incidence and mortality outcomes were included. Dose–response meta-analyses were performed by generalized least-squares estimation and restricted cubic splines with three knots located at the 10th, 50th, and 90th percentiles.ResultsA total of 25 cohort studies involving 1,300,263 participants were included. Conventional meta-analysis showed that hyperuricemia was significantly associated with stroke incidence (RR = 1.20, 95%CI: 1.11–1.29) and mortality (RR = 1.36, 95%CI: 1.17–1.58). Subgroup analysis indicated that hyperuricemia significantly increased the risks of stroke incidence (RR = 1.22, 95%CI: 1.08–1.38) and mortality (RR = 1.42, 95%CI: 1.15–1.77) among women. Regarding stroke subtype, hyperuricemia was significantly associated with the incidence (RR = 1.21, 95%CI: 1.03–1.42) and mortality (RR = 1.23, 95%CI: 1.01–1.49) of ischemic stroke. A J shaped dose–response relationship was found between uric acid and stroke incidence (p = 0.0023), with risk rising across uric acid levels from104 to 764.5 μmol/L and a nadir at 225 μmol/L, whereas no significant nonlinear relationship was observed for stroke mortality.ConclusionHyperuricemia is associated with increased risks of stroke incidence and mortality, especially in women and ischemic stroke. A J-shaped dose–response relationship was observed for stroke incidence, but not for stroke mortality. Monitoring uric acid levels and their longitudinal changes may be valuable in stroke prevention strategies.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261394403, identifier PROSPERO (CRD420261394403).]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1889769</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1889769</link>
        <title><![CDATA[Anti-amyloid treatment in Alzheimer disease: updated implications for patients with cerebral amyloid angiopathy and other cerebrovascular conditions]]></title>
        <pubdate>2026-08-19T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Matija Zupan</author><author>Polona Rus Prelog</author><author>Milica Gregorič Kramberger</author><author>Senta Frol</author>
        <description><![CDATA[Anti-amyloid treatment (AAT) with monoclonal antibodies represents a major therapeutic advance in early Alzheimer disease (AD), but its introduction has important and underappreciated implications for vascular neurology. Because many patients with AD also have cerebral amyloid angiopathy and other cerebrovascular pathology, AAT influences stroke diagnosis, acute reperfusion therapy, and long-term antithrombotic management. Clinical trials of lecanemab and donanemab enrolled highly selected patients with minimal baseline cerebrovascular pathology, limiting generalizability to real-world populations with prevalent vascular comorbidity. Amyloid-related imaging abnormalities, particularly vasogenic edema and microhemorrhages, constitute a central safety concern and may clinically mimic acute ischemic stroke, complicating emergency decision-making and increasing the risk of inappropriate intravenous thrombolysis (IVT). Emerging reports of intracerebral hemorrhage following IVT in treated patients underscore the need for revised acute stroke pathways and support consideration of mechanical thrombectomy when otherwise indicated, although AAT-specific safety data are lacking. Beyond the hyperacute phase of stroke, concomitant use of anticoagulants or dual antiplatelet therapy raises unresolved questions regarding hemorrhagic risk, particularly in patients with atrial fibrillation or those requiring complex antithrombotic regimens. Alternative strategies, including left atrial appendage closure, may be considered in selected patients, although evidence in AAT recipients remains limited. As AAT enters routine practice, multidisciplinary collaboration, dedicated imaging protocols, and prospective safety registries will be essential to integrate disease-modifying AD treatment with safe and effective cerebrovascular care.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1843954</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1843954</link>
        <title><![CDATA[Transcranial Doppler for internal carotid artery stenting: rationale and design of a randomized controlled trial]]></title>
        <pubdate>2026-08-18T00:00:00Z</pubdate>
        <category>Study Protocol</category>
        <author>Yan Wang</author><author>Ying-Jia Wang</author><author>Lu Wang</author><author>Ting-Ting Wang</author><author>Hui-Sheng Chen</author>
        <description><![CDATA[BackgroundCarotid artery stenting (CAS) is an effective revascularization procedure for internal carotid artery stenosis, but it is associated with a high incidence of perioperative cerebral embolism, with asymptomatic and symptomatic embolic events occurring in up to 40% of patients. Transcranial Doppler (TCD) has been shown to enhance fibrinolysis through sonothrombolysis and may reduce embolic burden during carotid interventions.AimsTo evaluate whether intraoperative and post-procedural TCD monitoring can reduce the number of new diffusion-weighted imaging (DWI) lesions after CAS in patients with severe internal carotid artery stenosis.Sample size estimatesA total of 232 patients are required to detect a 50% reduction in the median number of new DWI lesions (from 2.0 to 1.0) with 80% power and a two-sided α of 0.05, accounting for a 5% dropout rate.DesignTCD-ICAS is a prospective, randomized, single-center, blinded endpoint trial. Patients scheduled for CAS are randomized 1:1 to receive either TCD treatment (1.6 MHz, 0.274 MPa) from femoral artery puncture until 30–60 min after procedure completion plus standard care, or standard care alone.OutcomesThe primary efficacy endpoint is the number of new DWI lesions at 24 h post-randomization. The primary safety endpoint is intracranial hemorrhage within 24 h.ConclusionThe TCD-ICAS trial will assess the efficacy and safety of TCD as an adjuvant therapy to reduce cerebral embolic events in patients undergoing CAS.Clinical trial registrationIdentifier (NCT07462546).]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1852619</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1852619</link>
        <title><![CDATA[Association between corpus callosum microstructure and upper limb motor outcome in moderate-to-severe ischemic stroke patients at 3–6 months post-stroke]]></title>
        <pubdate>2026-08-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jaeun Koo</author><author>Ah Yeon Lee</author><author>Eunjoo Lee</author><author>So-Youn Chang</author><author>Youngkook Kim</author>
        <description><![CDATA[BackgroundCorticospinal tract (CST) integrity is a well-established imaging correlate of post-stroke motor outcome but does not fully explain interindividual variability, particularly in moderate-to-severe impairment. The corpus callosum (CC) may provide complementary structural information. This study examined whether early subacute callosal microstructure is associated with upper limb motor outcome and recovery.MethodsWe retrospectively analyzed 38 patients with moderate-to-severe middle cerebral artery stroke who underwent diffusion tensor imaging during the early subacute phase. Fractional anisotropy (FA) values of the CST and CC were obtained. Upper limb motor function was assessed using the Shoulder Abduction and Finger Extension (SAFE) score. Simple linear regression and hierarchical multiple linear regression analyses examined associations of corrected CC FA (CC-FA ~ corrected~) with SAFE scores and ΔSAFE (change in SAFE score from baseline to 6 months).ResultsCST FA laterality index (CST FALI), lesion volume, and CC-FA ~ corrected~ were significantly associated with SAFE scores at 3 and 6 months post-stroke. In hierarchical multiple regression models, CC-FA ~ corrected~ of the genu showed a consistent nominal incremental contribution beyond CST FALI, age, and lesion volume at both timepoints (3 months: ΔR2 = 0.061, adjusted R2 = 0.600; 6 months: ΔR2 = 0.065, adjusted R2 = 0.646), though these findings require confirmation in larger prospective cohorts. The body and splenium did not reach statistical significance after accounting for these covariates. In exploratory analysis, CC-FA ~ corrected~ of the genu was the only variable significantly associated with ΔSAFE (R = 0.396, p = 0.041); CST FALI was not (p = 0.097).ConclusionCC-FA ~ corrected~ of the genu showed a consistent nominal association with upper limb motor outcome beyond CST integrity in moderate-to-severe stroke, suggesting a complementary role of callosal microstructure alongside CST integrity, with an exploratory association also observed for the magnitude of motor improvement over time. Early combined assessment of CC and CST integrity during the subacute phase may provide preliminary information regarding post-stroke motor outcomes.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1916069</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1916069</link>
        <title><![CDATA[Beyond the golden hour: prehospital delay and in-hospital stroke mortality in an elderly cohort reaching a national emergency-medicine center in Kazakhstan]]></title>
        <pubdate>2026-08-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Aigul A. Abduldayeva</author><author>Aliya M. Omarbek</author><author>Gulnur N. Doszhanova</author><author>Yerzhan B. Adilbekov</author><author>Nikolay A. Safonov</author><author>Saule A. Iskakova</author>
        <description><![CDATA[Stroke remains a leading cause of death and disability worldwide, and the “time-is-brain” paradigm frames prehospital speed as the principal modifiable determinant of outcome. Data from Kazakhstan, a country of about 2.72 million km2 with a population density of roughly 7 inhabitants per km2, are scarce, and it is unclear whether time metrics retain their prognostic role where most patients present outside reperfusion windows. We retrospectively analyzed 149 elderly patients (aged 57–75 years) with neuroimaging-confirmed acute stroke admitted to the National Coordination Center for Emergency Medicine (Astana, Kazakhstan) in 2025–2026; transient ischaemic attacks were excluded. Prehospital time, transport mode, reperfusion, neurological severity (NIHSS), comorbidity and in-hospital mortality were assessed using Spearman correlation, ANOVA and logistic regression. Ischemic stroke predominated (122/149; 81.9%). The median onset-to-door time was 9.5 h (IQR 3.0–48.3 h; range 25 min to 264 h), and only 36.5% arrived within the 4.5-h thrombolysis window; delays were longest in hemorrhagic stroke (median 24.8 h). Reperfusion therapy reached 24.6% of ischemic-stroke patients (thrombolysis 9.0%, thrombectomy 15.6%), whereas 67.2% were managed conservatively. Despite these delays, in-hospital mortality was low (6.8%). Onset-to-door time predicted neither in-hospital death (adjusted OR 1.00 per hour; p = 0.99) nor discharge functional status (modified Rankin Scale r = −0.013, p = 0.87); in a pre-specified Firth penalized model the predictors of death were baseline NIHSS (penalized OR 1.22 per point; 95% profile-likelihood CI 1.12–1.37; p < 0.001) and cardiac arrhythmia (penalized OR 5.51; 95% CI 1.07–29.71; p = 0.041). The crude mortality contrast (29.4% vs. 3.8%) is descriptive and hypothesis-generating. Baseline NIHSS was inversely correlated with onset-to-door time (r = −0.193; p = 0.019), indicating that later-presenting patients were less severely affected. These findings apply specifically to elderly patients who survived to reach the center and are not causal: the severity–time and time–mortality associations reflect who reaches the center. Within this hospital-admitted cohort, in-hospital mortality appears governed by neurological severity and cardiac comorbidity rather than transport time, supporting risk-based triage, arrhythmia detection, regionalized routing and air-ambulance capacity alongside efforts to compress door times.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1911042</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1911042</link>
        <title><![CDATA[Systemic immune-inflammation index, stress hyperglycemia ratio and triglyceride-glucose index in acute ischemic stroke: an integrated inflammation–stress–metabolism perspective]]></title>
        <pubdate>2026-08-14T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Xin Lin</author><author>Baoai Wang</author>
        <description><![CDATA[BackgroundAcute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide. Increasing evidence suggests that secondary brain injury after AIS is not driven by a single pathological process but results from the complex interaction among neuroinflammation, acute metabolic stress, and chronic metabolic dysfunction. The systemic immune-inflammation index (SII), stress hyperglycemia ratio (SHR), and triglyceride-glucose (TyG) index have emerged as readily available biomarkers reflecting these distinct yet interconnected pathophysiological pathways.ObjectiveTo review the current evidence regarding the associations of SII, SHR, and TyG with disease severity, functional outcomes, and stroke-related complications in AIS, and to explore their complementary value within an integrated inflammation–stress–metabolism framework.MethodsThis narrative review summarized relevant clinical and mechanistic studies investigating SII, SHR, and TyG in patients with AIS. Evidence was identified primarily through PubMed and supplemented by manual screening of reference lists.ResultsCurrent evidence indicates that elevated SII is closely associated with inflammatory activation, stroke severity, poor functional outcomes, mortality, and various stroke-related complications. SHR reflects relative hyperglycemia induced by neuroendocrine stress and is associated with early neurological deterioration, hemorrhagic complications, cerebral edema, and adverse prognosis. As a surrogate marker of insulin resistance, TyG is associated with stroke severity, poor neurological recovery, recurrent stroke, and chronic vascular injury. Although these biomarkers originate from different biological pathways, inflammation, stress hyperglycemia, and insulin resistance interact extensively throughout the progression of AIS. Consequently, SII, SHR, and TyG provide complementary information regarding inflammatory burden, acute metabolic stress, and chronic metabolic vulnerability.ConclusionSII, SHR, and TyG represent three interrelated yet distinct dimensions of AIS pathophysiology. Integrating these biomarkers may provide a more comprehensive assessment of patient risk than any single indicator alone and may improve risk stratification and prognostic evaluation. Future prospective studies are warranted to validate their combined predictive value and establish integrated risk assessment models for AIS.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1824344</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1824344</link>
        <title><![CDATA[The impact of stroke on intramuscular connective tissue in mice]]></title>
        <pubdate>2026-08-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Xiaoxiao Zhao</author><author>Giulio Morri</author><author>Matteo D’Urso</author><author>Caterina Fede</author><author>Lucia Petrelli</author><author>Livia Vignozzi</author><author>Yunfeng Sun</author><author>Claudia Clair</author><author>Gabriele Deidda</author><author>Preeti Raghavan</author><author>Manuela Allegra</author><author>Carla Stecco</author>
        <description><![CDATA[BackgroundPrevious studies about post-stroke peripheral structural remodeling have been focused on muscle fiber alterations, while extracellular matrix (ECM) remodeling in musculoskeletal tissues remains unclear. This study examines changes in extracellular matrix (ECM), specifically hyaluronan (HA) and collagen, in forelimb muscles following distal middle cerebral artery occlusion (dMCAO) in mice.MethodsTwenty-two 8-week-old C57BL/6 mice (10 male, 12 female) were randomly assigned to the control group (n = 10; 4 male, 6 female) or the experimental group (n = 12; 6 male, 6 female). 4 weeks post-stroke, forelimb muscle samples were collected and analyzed for HA and collagen distribution and concentrations.ResultsHA concentrations were significantly elevated in both the left (stroke affected) forelimb muscles (63.74 ± 11.80 μg/g), and right (unaffected) forelimb muscles (64.16 ± 13.52 μg/g) of stroke mice compared to the controls (left: 50.07 ± 8.84 μg/g, p = 0.022; and right: 49.36 ± 12.22 μg/g, p = 0.015). No significant difference in HA levels was observed between the affected and unaffected sides of stroke mice (p = 0.905). Collagen concentrations did not differ significantly among groups (control left: 8.62 ± 2.91 μg/g; control right: 8.77 ± 1.35 μg/g; stroke-affected: 8.24 ± 2.11 μg/g; stroke-unaffected: 8.28 ± 2.45 μg/g).ConclusionThe results revealed a systemic increase in HA concentration in the stroke group, while collagen levels remained unchanged. These findings provide biochemical evidence of early alterations in extracellular matrix composition after stroke.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1899933</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1899933</link>
        <title><![CDATA[Adjuvant neuroprotective therapies for acute ischemic stroke in the reperfusion era: a comparative narrative review of clinical evidence for edaravone, edaravone-dexborneol, and butylphthalide]]></title>
        <pubdate>2026-08-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Weiqing Wang</author><author>Junsen Ye</author>
        <description><![CDATA[Reperfusion therapies, including intravenous thrombolysis and endovascular treatment (EVT), are central to acute ischemic stroke (AIS) management; however, ischemia–reperfusion injury may limit recovery despite successful recanalization. This structured narrative review compares the clinical evidence, safety signals, and mechanistic literature for edaravone, butylphthalide (NBP), and the fixed-dose combination edaravone-dexborneol (EDB) as adjunctive neuroprotective approaches. The evidence base is heterogeneous with respect to population, background reperfusion treatment, outcome timing, and geographical setting. In TASTE-2, EDB administered before EVT was associated with a modest increase in 90-day functional independence versus placebo (55.0% vs. 49.6%, p = 0.05), without an apparent safety signal; bridging alteplase was permitted in a subset of participants. In the BAST trial, NBP improved the prespecified 90-day functional outcome versus placebo among patients receiving intravenous thrombolysis and/or EVT (56.7% vs. 44.0%). Observational studies and meta-analyses provide supportive but non-confirmatory evidence for edaravone. Network meta-analyses generate relative rankings at individual endpoints, but indirect comparisons and differing outcome networks preclude definitive between-agent selection. Mechanistic studies indicate overlapping antioxidant, anti-inflammatory, mitochondrial, and neurovascular effects rather than exclusive pathway regulation. Biomarker and imaging approaches, including exploratory GFAP and UCH-L1 measurements, are promising research tools but are not yet validated for treatment selection in AIS. Accordingly, these agents should be regarded as candidates for further evidence-informed adjunctive use; future trials are needed to define reproducible patient-selection and treatment-timing strategies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1824565</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1824565</link>
        <title><![CDATA[Do conventional intracerebral hemorrhage functional scores apply to mild-to-moderate hemorrhage?]]></title>
        <pubdate>2026-08-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ao Chen</author><author>Jiaying Peng</author><author>Liang Guo</author><author>Renhui Zhou</author>
        <description><![CDATA[BackgroundConventional intracerebral hemorrhage (ICH) functional scores are typically developed based on clinical factors for assessing mortality risk, and their applicability in evaluating functional outcomes in patients with the specific hemorrhagic subtype of mild to moderate ICH(MTM-ICH) remains unclear. Therefore, we aimed to construct a nomogram model to predict early functional dependence in this patient population and to validate three previous general ICH functional scores.MethodsWe conducted a retrospective analysis of data from 575 patients with MTM-ICH (GCS score ≥ 9) treated at our hospital between January 2018 and July 2025. The baseline demographic information, clinical characteristics, and clinical outcomes were collected. Early functional dependence was defined as a modified Rankin Scale (MRS) score ≥ 3 at discharge or 30 days after ICH. Least absolute shrinkage and selection operator (LASSO) and stepwise logistic regression analyses were used to screen for risk factors for early functional dependence and construct a predictive model. The model was visualized using a nomogram, and its predictive performance was compared with three existing ICH functional scores (FUNC, ICH-GS and ICH-FOS). Internal validation of the nomogram was performed using a 10-fold cross-validation combined with bootstrap resampling.ResultsAmong 575 patients with MTM-ICH, 198 (34.4%) developed early functional dependence. LASSO and stepwise logistic regression analyses identified six independent predictors: age, admission GCS score, hematoma volume, thalamic hemorrhage, basal ganglia hemorrhage, and mechanical ventilation. The nomogram based on these factors demonstrated good calibration and superior predictive performance compared to three existing ICH functional scores (AUC = 0.856 for our nomogram, 0.579 for FUNC, 0.601 for ICH-GS, and 0.714 for ICH-FOS, respectively). The decision curve analysis further demonstrated that the model had greater net benefit than the three previous general ICH functional scores. Internal validation confirmed the model’s stability and generalizability (10-fold cross-validation mean: 0.846; bootstrap-corrected C-index: 0.844).ConclusionAmong patients with MTM-ICH, advanced age, lower admission GCS score, larger hematoma volume, thalamic or basal ganglia hemorrhage, and mechanical ventilation were associated with a higher risk of early functional dependence. The nomogram developed based on these factors demonstrated high predictive performance. In contrast, conventional ICH functional scores demonstrate certain limitations when assessing this specific hemorrhage subtype.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1847958</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1847958</link>
        <title><![CDATA[β-Hydroxybutyrate induces microglial M2 polarization by inhibiting the NF-κB/NLRP3 pathway to ameliorate cerebral ischemia–reperfusion injury]]></title>
        <pubdate>2026-08-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Qiong Chen</author><author>Shui Cheng</author><author>Chang Huang</author><author>Ruping Xiang</author>
        <description><![CDATA[ObjectiveTo investigate the neuroprotective effects of β-hydroxybutyrate (BHB) on cerebral ischemia–reperfusion injury (CIRI) and its underlying molecular mechanisms; to clarify the association between ketone bodies and the severity of CIRI under obese conditions.MethodsCIRI rat model was established using modified middle cerebral artery occlusion/reperfusion (MCAO/R), while obesity was induced using high fat diet. BHB was administered via subcutaneous osmotic pumps. Lipopolysaccharide (LPS) was intraperitoneally injected to forcibly activate the nuclear factor-κB (NF-κB)/NOD-like receptor protein 3 (NLRP3) pathway. Neurological deficits were evaluated using the Zea–Longa 5-point scoring system. Serum BHB levels were measured by colorimetric assay. Immunofluorescence was performed to detect CD86 (M1 phenotype) and CD206 (M2 phenotype) levels. Inflammatory cytokines in brain tissues were measured. Levels of phosphorylated p65 (p-p65), cleaved caspase-1, and ionized calcium-binding adapter molecule 1 (Iba1) were analyzed by Western blotting.ResultsCIRI rats with obesity exhibited increased serum BHB levels, reduced neurological deficit scores, and markedly decreased infarct volumes. Moreover, levels of p-p65, cleaved caspase-1, Iba1, and pro-inflammatory cytokines, were decreased, while Iba1+CD206+ co-localization was increased. BHB treatment for CIRI rats with normal weight reduced neurological deficit scores, increased serum BHB, and decreased infarct volume. Following further LPS administration, neurological deficit scores and infarct volume were enhanced, with no difference in serum BHB levels.ConclusionElevated endogenous BHB under obese conditions exerts neuroprotective effects against CIRI, and exogenous BHB can mimic this effect. Mechanistically, BHB inhibits activation of the NF-κB/NLRP3 pathway and promotes microglial polarization toward the anti-inflammatory M2 phenotype, thereby alleviating CIRI.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1819400</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1819400</link>
        <title><![CDATA[AngioPLUS-derived carotid intraplaque neovascularization predicts recurrent anterior circulation stroke: a prospective cohort study]]></title>
        <pubdate>2026-08-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Hao Zhang</author><author>Jun He</author><author>Jimei Xu</author><author>Rongfeng Wang</author><author>Shugang Cao</author><author>Mingwu Xia</author>
        <description><![CDATA[Background and purposeThe predictive value of carotid intraplaque neovascularization (IPN), assessed by the novel AngioPLUS technique, for recurrent anterior circulation ischemic stroke (ACIS) remains unclear. This study aimed to evaluate the prognostic value of IPN for stroke recurrence in patients with ACIS and to develop a parsimonious prediction model by screening core predictors using Lasso regression, with subsequent assessment of its discrimination, calibration, and clinical utility.MethodsConsecutive patients admitted for ACIS who underwent IPN assessment using AngioPLUS ultrasound between August 2020 and February 2025 were prospectively enrolled. Independent predictors of recurrent ischemic stroke were identified using Cox proportional hazards regression models. Least absolute shrinkage and selection operator (Lasso) regression was employed to screen core predictors for constructing a parsimonious Cox model. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) curves, and internal validation was performed with Bootstrap resampling B=1000 to calculate the concordance index (C-index). Model calibration was assessed using calibration plots. Risk stratification was conducted based on the optimal cut-off value of the total nomogram score, and differences in survival between groups were compared using the Kaplan–Meier method and the log-rank test.ResultsA total of 143 patients (93 males, 65.0%; mean age 67.6 ± 11.7 years) with a median follow-up of 21 months (range 6–56 months) were enrolled, during which 26 patients experienced recurrent ischemic stroke. The recurrence rate was significantly higher in the high IPN group compared to the low IPN group (35.0% vs. 6.0%, p < 0.001). Lasso regression identified two core predictors: IPN Grades 2 (HR = 5.30, 95% CI 1.99–14.08, p < 0.001) and LDL-C (HR = 2.23, 95% CI 1.41–3.52, p < 0.001). The parsimonious model yielded a concordance index (C-index) of 0.786 (95% CI 0.707–0.866), with time-dependent AUC values of 0.716, 0.809, and 0.815 at 12, 24, and 36 months, respectively. Calibration plots closely approximated the ideal diagonal line. Nomogram-based risk stratification demonstrated that patients in the high-risk group had significantly lower recurrence-free survival rates at 12, 24, and 36 months (80.46, 36.40, and 28.31%, respectively) compared to those in the low-risk group (97.73, 90.80, and 88.21%, respectively). The median survival time was 23.0 months in the high-risk group and was not reached in the low-risk group (log-rank p < 0.001).ConclusionCarotid IPN is an independent predictor of ACIS recurrence. A parsimonious Cox model incorporating IPN Grades 2 and LDL-C demonstrated favorable discrimination and calibration. The nomogram based on this model effectively identifies individuals at high risk of recurrence, offering a simple and practical tool for guiding individualized secondary prevention strategies in clinical practice.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1861639</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1861639</link>
        <title><![CDATA[Impact of non-amyloid cerebral small vessel disease on the efficacy and safety of argatroban in acute ischemic stroke: a retrospective cohort study]]></title>
        <pubdate>2026-08-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Fen Liu</author><author>Qiang Wu</author><author>Yan Lin</author><author>Jie Chen</author>
        <description><![CDATA[ObjectiveTo investigate whether imaging features of non-cerebral amyloid angiopathy cerebral small vessel disease (non-amyloid CSVD) influence the efficacy of argatroban in acute ischaemic stroke (AIS) and to test for effect modification.MethodsPatients with AIS admitted to Songxi County Hospital from January 2022 to December 2023 were enrolled and divided into an argatroban group and a control group. CSVD imaging markers (multiple lacunar infarcts, multiple subcortical white matter lesions, white matter hyperintensities, and brain atrophy) were assessed. Multivariable logistic regression was used to analyse favourable outcome at 90 days (modified Rankin Scale score 0–2), and interaction terms were introduced to test for effect modification.ResultsA total of 139 patients were included (66 in the argatroban group, 73 in the control group). Argatroban reduced early neurological deterioration (adjusted OR 0.045, p = 0.004), but no significant difference was observed in the rate of favourable outcome at 90 days between the two groups (80.3% vs. 79.5%, p = 0.208). Severe white matter hyperintensities modified the efficacy of argatroban (p for interaction < 0.10), with greater benefit seen in patients without severe white matter hyperintensities. Only one intracranial haemorrhage occurred, and it was in the control group.ConclusionIn patients with AIS after exclusion of cerebral amyloid angiopathy, argatroban improves early neurological function but does not improve functional outcome at 90 days. Severe white matter hyperintensities may be potential effect modifiers, generating hypotheses for imaging-based treatment stratification that warrant prospective validation.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1791832</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1791832</link>
        <title><![CDATA[Association between the Fibrosis-4 index and stroke and related outcomes: a meta-analysis]]></title>
        <pubdate>2026-08-10T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>Wei Lai</author><author>Haojie Yu</author><author>Hongming Wang</author>
        <description><![CDATA[ObjectiveThis meta-analysis evaluated the associations between the Fibrosis-4 index (FIB-4) and overall stroke, ischemic stroke, hemorrhagic outcomes, poor functional outcome, and all-cause mortality.MethodsPubMed, Embase, and the Cochrane Library were searched from inception to November 4, 2025. Cohort and cross-sectional studies evaluating categorical or continuous FIB-4 were eligible. Quantitative syntheses were stratified by outcome, FIB-4 modeling approach, and effect measure, with odds ratios (ORs) and hazard ratios (HRs) analyzed separately. Prediction intervals were calculated for random-effects analyses containing at least three independent estimates.ResultsTwenty-two studies, including 20 cohort studies and two cross-sectional studies, were included, of which 20 contributed to at least one quantitative synthesis. Elevated categorical FIB-4 was associated with greater odds of overall stroke (OR = 1.86, 95% CI: 1.63–2.14), ischemic stroke (OR = 2.03, 95% CI: 1.72–2.40), symptomatic intracranial hemorrhage (OR = 2.52, 95% CI: 1.79–3.53), poor functional outcome (OR = 2.88, 95% CI: 2.47–3.35), and all-cause mortality (OR = 2.98, 95% CI: 2.51–3.53). Continuous FIB-4 was also associated with overall stroke (HR = 1.08, 95% CI: 1.02–1.14), symptomatic intracranial hemorrhage (OR = 1.33, 95% CI: 1.20–1.48), poor functional outcome (OR = 1.26, 95% CI: 1.11–1.43), and all-cause mortality (HR = 1.08, 95% CI: 1.03–1.12). However, prediction intervals crossed the null for the continuous analyses of poor functional outcome and all-cause mortality, and the categorical overall-stroke analysis was exploratory.ConclusionHigher FIB-4 was associated with stroke and adverse stroke-related outcomes across several observational analyses. FIB-4 may provide adjunctive risk information, but prospective validation and formal assessment of its incremental clinical value are required before routine implementation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/search, identifier: CRD420251207801.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1849476</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1849476</link>
        <title><![CDATA[Prognostic value of the CALLY index for functional outcomes in acute ischemic stroke: a systematic review and exploratory quantitative synthesis]]></title>
        <pubdate>2026-08-07T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>Zongyu Cai</author><author>Shihuan Zhong</author><author>Yifan Liang</author>
        <description><![CDATA[BackgroundThe C-reactive protein-albumin-lymphocyte (CALLY) index is a novel composite biomarker reflecting systemic inflammation, nutritional status, and immune function. Emerging evidence suggests its potential prognostic value in acute ischemic stroke (AIS). However, no systematic analysis has been conducted to evaluate its association with functional outcomes in AIS patients. This systematic review with exploratory quantitative synthesis aimed to assess the prognostic value of the CALLY index for functional outcomes in AIS.MethodsWe systematically searched the Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to March 2026. The search was initially conducted in February 2025 and updated in March 2026 prior to submission. Observational studies evaluating the association between the CALLY index and functional outcomes in AIS patients were included. The primary outcome was poor functional outcome defined by the modified Rankin Scale (mRS), with poor outcome defined as mRS ≥ 2, mRS > 2, or mRS ≥ 3 at 3 months. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity was evaluated using Cochran’s Q test and I2 statistic.ResultsThree studies involving 1,161 AIS patients were included. The exploratory quantitative synthesis revealed that a higher CALLY index was significantly associated with a lower risk of poor functional outcome (pooled OR = 0.766, 95% CI: 0.695–0.845, p < 0.001), with no significant heterogeneity across studies (I2 = 0.0%, Q = 1.33, p = 0.516). All included studies were of high quality (NOS scores 8-9). Publication bias could not be reliably assessed due to the limited number of included studies.ConclusionThis systematic review with exploratory quantitative synthesis provides preliminary pooled evidence suggesting that the CALLY index may be a potential predictor of functional outcome in AIS patients. A higher CALLY index was associated with a lower risk of poor functional outcomes. However, given the limited number of included studies (only three retrospective studies from China), these findings should be considered hypothesis-generating rather than confirmatory and require validation in large-scale, multicenter, prospective studies across diverse populations before clinical application.Systematic review registrationThe review was registered in PROSPERO: CRD420261350196 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261350196.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1904486</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1904486</link>
        <title><![CDATA[Intravenous thrombolysis in acute ischemic stroke after recent direct oral anticoagulant intake: toward evidence-informed care]]></title>
        <pubdate>2026-08-06T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Matija Zupan</author><author>Mišo Šabovič</author><author>Pawel Kermer</author><author>Senta Frol</author>
        <description><![CDATA[The use of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with recent direct oral anticoagulant (DOAC) intake remains one of the most debated issues in contemporary stroke medicine. Current international guidelines generally discourage IVT within 48 h of DOAC ingestion, largely because of concerns regarding symptomatic intracranial hemorrhage (sICH) and the absence of randomized evidence. However, an increasing body of evidence from international registries and multicenter cohorts has not identified a clear increase in sICH among carefully selected patients with recent DOAC exposure who received IVT. Some observational studies have also reported an association with more favorable functional outcomes than those observed in otherwise eligible patients in whom reperfusion therapy was withheld, although these comparisons are susceptible to selection bias and confounding by indication. In this Perspective, we discuss recent advances that have challenged the traditional practice of broadly excluding patients with recent DOAC exposure from IVT. We review observational evidence concerning IVT in selected patients, examine biological hypotheses that could be relevant to the observed clinical findings, and discuss evolving roles of reversal agents and laboratory assessment of anticoagulant activity. We further highlight current implementation barriers and future research priorities, including prospective studies, improved point-of-care anticoagulant testing, and refinement of patient-selection strategies. We argue that contemporary evidence supports reconsideration of rigid time-based exclusion criteria in favor of more individualized, evidence-informed decision-making. Although important uncertainties remain, recent DOAC exposure may not necessarily preclude IVT in appropriately selected patients, particularly when anticoagulant activity can be reliably assessed.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fneur.2026.1945724</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fneur.2026.1945724</link>
        <title><![CDATA[Correction: High-altitude exposure and ischemic stroke: pathophysiological mechanisms and current perspectives]]></title>
        <pubdate>2026-08-06T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Yuhuan Qiao</author><author>Yuding Luo</author><author>Yu Hu</author><author>Chuanxi Duan</author><author>Junhao Li</author><author>Xiaojing Luo</author><author>Jian Wang</author>
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