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Neurology International
Special Issues
Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery
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Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery

A special issue of Neurology International (ISSN 2035-8377). This special issue belongs to the section "Movement Disorders and Neurodegenerative Diseases".

Deadline for manuscript submissions: 31 March 2026 | Viewed by 2626

Special Issue Editor

Dr. Sonu M. M. Bhaskar

E-Mail Website
Guest Editor
1. Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
2. Global Health Neurology Lab and NSW Brain Clot Bank, Sydney, Australia
Interests: cerebrovascular disorders; stroke; biomarkers; social inequalities in health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The treatment of acute ischemic stroke has altered significantly with the advent of reperfusion therapies, yet critical challenges related to the optimization of neuroprotection, the mitigation of secondary injury, and the enhancement of post-stroke recovery remain. This Special Issue, entitled "Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery", aims to present cutting-edge advancements that address these challenges and redefine stroke care, from hyperacute intervention to long-term functional restoration.

This Special Issue will explore the latest breakthroughs in thrombolysis, endovascular thrombectomy, and adjunctive neuroprotective strategies, providing mechanistic insights into ischemia–reperfusion injury, blood–brain barrier dysfunction, and inflammatory cascades. We particularly encourage contributions that address emerging molecular targets for neuroprotection, novel imaging biomarkers for precision therapy, and the integration of artificial intelligence into treatment decision-making.

Additionally, we seek high-impact studies on post-stroke recovery, including neuroplasticity-driven rehabilitation, brain–computer interfaces, neuromodulation, and personalized strategies that prevent stroke-related cognitive impairment. This Special Issue will particularly focus on translational research that integrates preclinical discoveries with real-world clinical applications, as well as approaches to health systems that reduce disparities and improve outcomes across diverse populations.

By compiling multidisciplinary articles concerning stroke pathophysiology, intervention, and recovery, this Special Issue aims to push the boundaries of stroke research and accelerate the transition toward precision medicine in cerebrovascular care.

Dr. Sonu M. M. Bhaskar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Neurology International is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stroke
  • reperfusion therapy
  • imaging
  • biomarkers
  • disease burden
  • pathophysiology
  • stroke care
  • neuroprotective
  • post-stroke recovery

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Related Special Issue

Published Papers (5 papers)

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Research

12 pages, 816 KB  
Article
Blood–Brain Barrier Dysfunction, Edema Formation and Functional Recovery in Ischemic and Hemorrhagic Stroke: A Retrospective Study
by Christian A. Müller, Jochen A. Sembill, Bernd Kallmünzer, Maximilian Bailer, Ludwig Singer, Tobias Engelhorn, Arnd Dörfler, Stefan Schwab, Stefanie Balk and Maximilian I. Sprügel
Neurol. Int. 2025, 17(11), 177; https://doi.org/10.3390/neurolint17110177 - 1 Nov 2025
Viewed by 217
Abstract
Objectives: We aimed to determine temporal patterns of blood–brain barrier (BBB) dysfunction, edema formation and functional recovery in acute stroke. Materials and Methods: Patients of two observational studies on ischemic and hemorrhagic stroke between 2006 and 2019 were analyzed. Blood–brain barrier dysfunction was [...] Read more.
Objectives: We aimed to determine temporal patterns of blood–brain barrier (BBB) dysfunction, edema formation and functional recovery in acute stroke. Materials and Methods: Patients of two observational studies on ischemic and hemorrhagic stroke between 2006 and 2019 were analyzed. Blood–brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio. Edema formation was measured on all available imaging scans during hospital stay. Relative edema was defined as the ratio of edema volume to stroke volume. Multivariable regression models were applied to analyze associations and calculate predicted probabilities. Results: Overall, 138 stroke patients, 103 (74.6%) with ischemic stroke and 35 (25.4%) with hemorrhagic stroke, were analyzed. The predicted probability of substantial BBB dysfunction was approximately 46 (37–55) % among patients analyzed on 1 day after symptom onset and declined with increasing time, thereafter reaching 10 (3–29) % on day 30. The maximal extent of edema was lower in ischemic versus hemorrhagic stroke (relative edema: 1.5 [1.2–1.8] vs. 2.6 [1.9–4.5], p = 0.003) and occurred earlier after stroke onset (5.9 [4.6–8.5] days vs. 12.3 [9.7–16.4] days, p = 0.009). BBB dysfunction was associated with increased edema formation (adjusted relative edema: 4.0 [2.8–4.5] vs. 2.3 [1.8–3.0], p = 0.037) and lower chances of functional recovery (20/48 [41.7%] vs. 51/90 [56.7%], adjusted Odds Ratio: 0.37 [0.16–0.88], p = 0.025) in both ischemic and hemorrhagic stroke patients. Conclusions: BBB dysfunction frequently occurred in acute ischemic and hemorrhagic stroke and was associated with secondary injury and worse clinical outcomes. Future studies should evaluate BBB dysfunction as a potential therapeutic target using advanced imaging techniques early after stroke onset. Edema formation was aggravated and prolonged in hemorrhagic versus ischemic stroke. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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34 pages, 7149 KB  
Article
Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD Study): A Comprehensive Meta-Analysis
by Muskaan Gupta, Kevin J. Spring, Roy G. Beran and Sonu Bhaskar
Neurol. Int. 2025, 17(11), 176; https://doi.org/10.3390/neurolint17110176 - 1 Nov 2025
Viewed by 244
Abstract
Background: Ischemic stroke (IS) remains a leading global cause of mortality, recurrence, and long-term disability, with survivors also at risk of post-stroke dementia (PSD) and cognitive impairment (PSCI). The precise impact of statin therapy across different IS populations, including those with cardioembolic/atrial fibrillation [...] Read more.
Background: Ischemic stroke (IS) remains a leading global cause of mortality, recurrence, and long-term disability, with survivors also at risk of post-stroke dementia (PSD) and cognitive impairment (PSCI). The precise impact of statin therapy across different IS populations, including those with cardioembolic/atrial fibrillation (CE/AF) strokes and patients with low-baseline low-density lipoprotein (LDL) cholesterol, remains unclear, as does the influence of statin timing, intensity, type, and solubility. Methods: We conducted the Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD) meta-analysis, synthesizing evidence from 51 studies (n = 521,126), to evaluate the association between post-stroke statin therapy and key outcomes: all-cause mortality, stroke recurrence, cognition, and C-reactive protein (CRP). PSD was defined as new, persistent cognitive decline meeting standard diagnostic criteria, and PSCI as measurable but sub-threshold cognitive deficits. Random-effects models were used, and certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: Statin therapy significantly reduced all-cause mortality within 3 months (OR 0.32), at 1 year (OR 0.35), and beyond 1 year (OR 0.56). Stroke recurrence was modestly reduced both within 1 year (OR 0.77) and after 1 year (OR 0.76). Statin use was associated with a lower risk of PSD (OR 0.74) but not PSCI overall. Benefits extended to CE/AF-related strokes and patients with low-baseline LDL cholesterol, both showing significantly lower mortality with statin use. Early initiation (<24 h) was linked with reduced recurrence, though effects of statin intensity, type, and solubility were inconsistent. Statins also significantly reduced CRP levels, underscoring anti-inflammatory and pleiotropic mechanisms. Conclusions: The ISMARDD study demonstrates that statins confer survival benefit and selective cognitive protection (notably reduced PSD risk) after ischemic stroke, with modest recurrence benefit, supporting their broad use in secondary prevention. These findings highlight the need for precision-guided approaches tailored to stroke subtype, pharmacogenomics, and treatment timing to optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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23 pages, 7111 KB  
Article
Pulmonary Embolism After Acute Ischaemic Stroke (PEARL-AIS): Global Prevalence, Risk Factors, Outcomes, and Evidence Grading from a Meta-Analysis
by Darryl Chen, Yuxiang Yang and Sonu M. M. Bhaskar
Neurol. Int. 2025, 17(10), 168; https://doi.org/10.3390/neurolint17100168 - 12 Oct 2025
Viewed by 440
Abstract
Objectives: Pulmonary embolism (PE) is an uncommon but potentially fatal complication of acute ischaemic stroke (AIS). Its global burden and prevention remain incompletely defined. We performed a systematic review and meta-analysis (PEARL-AIS) to estimate prevalence, risk factors, outcomes, and prophylactic efficacy, with GRADE [...] Read more.
Objectives: Pulmonary embolism (PE) is an uncommon but potentially fatal complication of acute ischaemic stroke (AIS). Its global burden and prevention remain incompletely defined. We performed a systematic review and meta-analysis (PEARL-AIS) to estimate prevalence, risk factors, outcomes, and prophylactic efficacy, with GRADE evidence appraisal. Methods: Following PRISMA 2020 and MOOSE guidelines, five databases (PubMed, Embase, Cochrane, Scopus, Web of Science) were searched (1995–2024). The protocol was prospectively registered (OSF s25ny). Random-effects models (DerSimonian–Laird; REML sensitivity) were used to pool prevalence and odds ratios; heterogeneity was evaluated with I2, Cochran’s Q, and τ2. Influence (leave-one-out) and subgroup analyses for prevalence and mortality of PE in AIS were explored. Bias was assessed using the Modified Jadad Scale; overall certainty was graded with the GRADE framework. Results: Twenty-four studies met the inclusion criteria (n = 25,666,067), of which seventeen studies (n = 23,637,708) contributed to pooled prevalence analyses. The pooled prevalence of PE after AIS was 0.40% (95% CI 0.33–0.49), approximately six-fold higher than in the general population, with considerable heterogeneity (I2 > 90%, Cochrane classification). The pooled mortality among AIS patients with PE was 12.9% (95% CI 1.6–31.7). Mortality risk was significantly higher in AIS patients with PE (OR 4.96, 95% CI 2.98–8.24). Atrial fibrillation (29%), cancer (19%), and smoking (23%) were common; hypertension (54%) and diabetes (23%) were prevalent but not predictive, with diabetes showing a paradoxical protective association (OR 0.88, 95% CI 0.84–0.92). Pharmacological prophylaxis was associated with a reduced risk of PE (OR 0.64, 95% CI 0.46–0.90; I2 = 0%), supported by moderate-certainty evidence. Conclusions: PE is an uncommon but often fatal complication of AIS. Traditional venous thromboembolism predictors underperform in this context, suggesting a stroke-specific thromboinflammatory mechanism linking the brain and lung axis. Despite considerable heterogeneity and low-to-moderate certainty of evidence, pharmacological prophylaxis demonstrates a consistent protective effect. Systematic PE surveillance and tailored prophylactic strategies should be integral to contemporary stroke care, while future studies should refine risk stratification and elucidate the mechanistic underpinnings of this brain–lung thromboinflammatory continuum. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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11 pages, 741 KB  
Article
Effect of Cilostazol in the Expression of Biomarkers and Neurological Outcome Following Experimentally Induced Cerebrovascular Accident—Experimental Protocol
by Christiana Anastasiadou, Stavroula Kastora, Alkistis Kapelouzou, Anastasios Papapetrou, Angelos Megalopoulos, Nikolaos Kostomitsopoulos, Efthymios Paronis, Andreas Lazaris, George Geroulakos, Christos Liapis, Nikolaos Saratzis and John Kakisis
Neurol. Int. 2025, 17(8), 126; https://doi.org/10.3390/neurolint17080126 - 11 Aug 2025
Viewed by 518
Abstract
Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and [...] Read more.
Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and combinatorial pre-treatment upon neurological status and biomarkers, namely protein S100b, GFAP, procalcitonin, and galectin-3, following stroke. Methods: Twelve-week-old Sprague–Dawley rats were randomly assigned to four groups, each containing six rats: control group (normal saline), cilostazol group (30 mg/kg/daily), aspirin group (10 mg/kg/daily), and aspirin/cilostazol group. Each substance was administered by gavage for four weeks. All animals were subjected to cerebral ischemia for 2 h using intraluminal middle cerebral artery occlusion. A neurological examination was performed, serum concentrations of biomarkers were determined, and the animals were then sacrificed. Results: All treatment groups exhibited variations in the severity of immediate neurological presentation. Unlike the control group, where all rats presented with severe focal neurology or mortality, most rats in the treatment groups displayed no to moderate focal neurology. Moreover, the aspirin/cilostazol group consistently exhibited significantly lower levels in the studied biomarkers compared to other groups. Conclusions: Co-administration of cilostazol and aspirin significantly ameliorates the immediate expression of the studied biomarkers. Further large-scale studies are needed to investigate the effect of combined therapy for primary and secondary prevention of stroke, using not only serum biomarkers but other specific clinical and laboratory endpoints. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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14 pages, 664 KB  
Article
The Association of Cerebral Blood Flow Measured Using Extracranial Carotid Ultrasound with Functional Outcomes in Patients with Anterior Circulation Large Vessel Occlusion After Endovascular Thrombectomy—A Retrospective Study
by Xin-Hong Lin, Kuan-Wen Chen, Chung-Fu Hsu, Ting-Wei Chang, Chao-Yu Shen and Hsin-Yi Chi
Neurol. Int. 2025, 17(5), 67; https://doi.org/10.3390/neurolint17050067 - 25 Apr 2025
Viewed by 759
Abstract
Background: Endovascular mechanical thrombectomy (EVT) is regarded as the standard treatment for acute ischemic stroke with large vessel occlusion. Few studies have examined the evolution of cerebral flow after the acute stage of ischemic stroke. In this study, we examined the association [...] Read more.
Background: Endovascular mechanical thrombectomy (EVT) is regarded as the standard treatment for acute ischemic stroke with large vessel occlusion. Few studies have examined the evolution of cerebral flow after the acute stage of ischemic stroke. In this study, we examined the association of functional outcomes with cerebral blood flow by extracranial carotid sonography during the subacute phase after EVT and multiple prognostic variables. Methods: We conducted a single-center, retrospective, observational study between January 2018 and June 2023. Patients with acute stroke resulting from anterior circulation large vessel occlusion who underwent EVT were included. All patients underwent carotid sonography in the second week after EVT. Patients with fair (modified Rankin Scale [mRS]: 0–3) and poor outcomes (mRS: 4–6) were compared to determine the association between and identify the predictors of these factors and functional outcomes. Results: A total of 89 patients were included (female: 38 (42.7%); mean age: 69.45 ± 13.59 years). Multivariable logistic regression analysis revealed that three factors were independent predictors of fair outcomes: (1) the Alberta Stroke Program Early CT Score (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.16–2.78; p = 0.009); (2) Thrombolysis in Cerebral Infarction 2b to 3 (OR: 4.91; 95%CI: 1.10–21.89; p = 0.037); (3) the ratio of treatment-side blood flow between the internal carotid artery and common carotid artery (QTI/QTC, OR: 45.35; 95% CI: 1.11–1847.51; p = 0.04). Conclusions: The ratio of QTI/QTC is a clinically relevant parameter as a potential predictor of favorable outcomes. This parameter can be used to formulate patient prognostic scores and help clinicians determine whether adequate cerebral perfusion is maintained during the subacute phase. Full article
(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)
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