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Brain Stroke Across the Lifespan: Mechanisms, Models, Translational Advances and Impacts Beyond the Brain

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 1050

Special Issue Editor


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Guest Editor
1. Faculty of Medicine & Dentistry, Queen Mary University of London, Malta Campus, VCT 2520 Victoria, Malta
2. Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
3. Padova Neuroscience Center (PNC), University of Padova, 35131 Padova, Italy
Interests: behavioral and neuropsychological testing; circuits and cellular neuroscience; cognitive and brain development; cognitive; affective and behavioral neuroscience; electrophysiology and optical imaging; focal lesions (stroke and tumors); neuro-stimulation; neuroscience methods; preclinical (animals) models; translational and clinical neuroscience
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Special Issue Information

Dear Colleagues,

Brain stroke is a leading cause of morbidity and mortality worldwide, resulting from a sudden disruption in the cerebral blood flow that leads to focal neurological deficits. It is primarily classified into two major subtypes: ischemic and hemorrhagic. Ischemic stroke, which accounts for approximately 85% of all cases, is caused by an occlusion of a cerebral blood vessel due to thrombosis or embolism. Hemorrhagic stroke, although less common, is typically more severe and arises from the rupture of a blood vessel, leading to bleeding within the brain parenchyma or the subarachnoid space. In addition, transient ischemic attacks (TIAs), often referred to as “mini-strokes”, involve temporary cerebral hypoperfusion without permanent infarction, yet are clinically significant as predictors of future stroke risk.

Stroke affects individuals across all stages of life, including neonates, children, and adults, with distinct etiologies, pathophysiology, and clinical outcomes associated with each age group. Perinatal and pediatric strokes are frequently underdiagnosed and understudied, often leading to delayed intervention and a lack of age-specific, evidence-based treatment guidelines. In adults, the advent of intravenous thrombolysis and endovascular thrombectomy has markedly improved outcomes in eligible patients. However, these interventions remain limited by strict time windows and accessibility, leaving many without effective acute treatment options.

While acute management has progressed, substantial gaps remain in our understanding of the mechanisms underlying long-term recovery, neuroprotection, and neurorestoration. Moreover, beyond focal brain injury, stroke induces widespread systemic effects, including the dysregulation of cardiovascular function, immune responses, and metabolic pathways. Both systemic inflammation and neuroinflammation are known to play critical roles in the progression of injury and the modulation of repair, yet their dynamics across different stroke subtypes and populations remain inadequately characterized. Furthermore, emerging research highlights the significance of the gut–brain axis in influencing post-stroke recovery and neuroinflammatory responses.

This research topic welcomes contributions that explore the impact of stroke on both the brain and peripheral systems. We encourage submissions focused on mechanistic studies, translational models, and clinical research that advance our understanding of stroke as a complex, multisystem condition. A deeper exploration of the interplay between cerebral injury, systemic physiology, and recovery processes is essential for the development of novel, effective therapeutic strategies across all age groups and stroke types.

For this Special Issue, we welcome original research articles and reviews relating to this field.

Dr. Gabriele Deidda
Guest Editor

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Keywords

  • stroke
  • brain
  • cerebral injury
  • post-stroke recovery
  • systemic physiology
  • models
  • therapeutic strategies

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Published Papers (1 paper)

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Research

22 pages, 6326 KB  
Article
Modulatory Potential of Alpinetin on Inflammation, Oxidative Stress, Apoptosis, and Mitochondrial Dynamics in a Rat Middle Cerebral Artery Occlusion Model of Ischemic Stroke
by Sitthisak Thongrong, Ratchaniporn Kongsui, Lars Klimaschewski and Jinatta Jittiwat
Int. J. Mol. Sci. 2025, 26(23), 11329; https://doi.org/10.3390/ijms262311329 - 24 Nov 2025
Viewed by 708
Abstract
Ischemic stroke initiates a complex cascade of pathophysiological events—including energy failure, excitotoxicity, oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction—that together lead to extensive neuronal damage. Effectively targeting these interconnected mechanisms is crucial for achieving neuroprotection. Alpinetin, known for its antioxidant, anti-inflammatory, and cytoprotective [...] Read more.
Ischemic stroke initiates a complex cascade of pathophysiological events—including energy failure, excitotoxicity, oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction—that together lead to extensive neuronal damage. Effectively targeting these interconnected mechanisms is crucial for achieving neuroprotection. Alpinetin, known for its antioxidant, anti-inflammatory, and cytoprotective properties, has shown promise as a potential therapeutic agent for cerebral ischemia in preliminary studies. However, the exact molecular mechanisms underlying its neuroprotective effects remain unclear. Therefore, this study aimed to investigate the multifaceted actions of alpinetin in a preclinically relevant right middle cerebral artery occlusion (Rt.MCAO) rat model, focusing on its impact on neuronal survival, inflammation, oxidative stress, apoptosis, and mitochondrial function. Forty male Wistar rats were randomly assigned to four groups: sham operation, Rt.MCAO + vehicle, Rt.MCAO + piracetam (250 mg/kg BW), and Rt.MCAO + alpinetin (100 mg/kg BW). We examined glial cell morphology, protein kinase B (Akt) expression, mitochondrial superoxide dismutase (MnSOD), myeloperoxidase (MPO), anti-apoptotic proteins, mitogen-activated protein kinase (p38 MAPK) and mitofusin-2 (Mfn2). Treatment with alpinetin for 3 days exerted robust neuroprotective effects by significantly reducing astrocytic and microglial activation through the downregulation of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), restoring Akt expression, decreasing MPO activity, and enhancing MnSOD activity. Additionally, alpinetin modulated apoptotic signaling by lowering pro-apoptotic markers Bcl-2 Associated X-protein (Bax) and caspase-3 while increasing the expression of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL). It also attenuated p38 MAPK activation and preserved mitochondrial integrity by mitigating the decline in Mfn2 levels. Overall, these findings highlight the therapeutic potential of alpinetin in targeting multiple pathological processes involved in ischemic brain injury, supporting its promise as an effective treatment for stroke. Full article
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