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Biomolecules
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Molecular Mechanisms and Therapeutic Potential of Extracellular Vesicles in Neurovascular...
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Molecular Mechanisms and Therapeutic Potential of Extracellular Vesicles in Neurovascular Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 1801

Special Issue Editor

Dr. Ji Chen Bihl

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
Interests: cerebrovascular disease; diabetes; Hypertension; stem cel; lmicrovesicles

Special Issue Information

Dear Colleagues,

Neurovascular diseases—including stroke, vascular dementia, diabetic cerebrovascular complications, and neuroinflammatory disorders—are driven by complex cellular interactions across the brain–vascular interface. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as critical mediators of this crosstalk, carrying bioactive cargo such as microRNAs, proteins, lipids, and mitochondrial components. Once considered cellular debris, EVs are now recognized as potent regulators of endothelial function, blood–brain barrier stability, neuroinflammation, and neuronal survival. Increasing evidence shows that dysregulated EV signaling contributes to neurovascular injury, while therapeutic EVs from stem cells, immune cells, and metabolic tissues offer promising avenues for neuroprotection and vascular repair.

This Special Issue highlights cutting-edge research into the molecular mechanisms by which EVs influence neurovascular biology. It also explores EVs’ translational potential as biomarkers, drug delivery vehicles, and mitochondrial or genetic therapeutics. By integrating insights from vascular biology, neuroscience, and regenerative medicine, the articles in this issue aim to advance the development of EV-based strategies for diagnosing, preventing, and treating neurovascular diseases.

Dr. Ji Chen Bihl
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 250 words) can be sent to the Editorial Office for assessment.

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. Biomolecules 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 2700 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

  • extracellular vesicles
  • neurovascular diseases
  • cellular communications
  • biomarkers
  • therapeutic targets

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Published Papers (2 papers)

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Review

25 pages, 924 KB  
Review
Extracellular Vesicles in the Gut–Vascular–Brain Axis: A Missing Mechanistic Link Between IBD and Stroke Risk
by Harshal Sawant, Erika L. Butcher, Ji Chen Bihl and Subha Arthur
Biomolecules 2026, 16(4), 577; https://doi.org/10.3390/biom16040577 - 14 Apr 2026
Viewed by 692
Abstract
Inflammatory bowel disease (IBD) is increasingly recognized as a systemic inflammatory disorder associated with elevated long-term risk of ischemic stroke, even among younger individuals without traditional vascular risk factors. Although chronic inflammation, endothelial dysfunction, and hypercoagulability partially explain this association, the biological mechanisms [...] Read more.
Inflammatory bowel disease (IBD) is increasingly recognized as a systemic inflammatory disorder associated with elevated long-term risk of ischemic stroke, even among younger individuals without traditional vascular risk factors. Although chronic inflammation, endothelial dysfunction, and hypercoagulability partially explain this association, the biological mechanisms linking intestinal inflammation to cerebral vascular injury remain incompletely defined. Extracellular vesicles (EVs), membrane-bound particles released by epithelial, immune cells and platelets, have emerged as potent mediators of intercellular communication in inflammatory states. In IBD, circulating EVs are enriched with pro-inflammatory cytokines, microRNAs, adhesion molecules, tissue factors, which are capable of promoting endothelial activation, blood–brain barrier disruption, immune-thrombosis and neuroinflammation. This review summarizes epidemiologic, vascular, and EV biology literature to propose a mechanistic framework in which EV-mediated signaling integrates intestinal inflammation with cerebrovascular vulnerability along the gut–vascular–brain axis. While direct causal evidence remains limited, converging mechanistic data supports biological plausibility and defines priorities for future experimental and translational investigation. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Potential of Extracellular Vesicles in Neurovascular Diseases)
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36 pages, 3556 KB  
Review
Neurovascular Unit-Derived Extracellular Vesicles as Regulators of Post-Stroke Pathology and Neurorestoration
by Brianna Powell, Michael Chopp, Zhenggang Zhang and Xianshuang Liu
Biomolecules 2026, 16(3), 365; https://doi.org/10.3390/biom16030365 - 28 Feb 2026
Viewed by 811
Abstract
Ischemic stroke is a leading cause of disability worldwide, marked by profound disruption of the neurovascular unit (NVU), a dynamic grouping of neurons, astrocytes, cerebral endothelial cells (CECs), microglia, pericytes, and oligodendrocytes. While acute stroke interventions such as tissue plasminogen activator and endovascular [...] Read more.
Ischemic stroke is a leading cause of disability worldwide, marked by profound disruption of the neurovascular unit (NVU), a dynamic grouping of neurons, astrocytes, cerebral endothelial cells (CECs), microglia, pericytes, and oligodendrocytes. While acute stroke interventions such as tissue plasminogen activator and endovascular thrombectomy address reperfusion, they fail to engage the prolonged and cell-specific processes critical for recovery. Extracellular vesicles (EVs), membrane-bound carriers of proteins, lipids, and nucleic acids, have emerged as key modulators of intercellular communication within the NVU. This review synthesizes current evidence on NVU-derived EVs as both regulators and effectors of post-stroke pathology and repair. We highlight the phase-specific roles of EVs in modulating blood–brain barrier (BBB) integrity, thrombosis, angiogenesis, neurogenesis, oligodendrogenesis, synaptic plasticity, and neuroinflammation. This review places special emphasis on how EV cargo reflects the state of their parent cells and how EV-mediated crosstalk orchestrates coordinated neurorestorative responses. We further discuss the dual nature of EVs, their therapeutic potential for stroke, and the methodological challenges impeding clinical translation, including isolation standardization, cell-specific targeting, and regulatory barriers. Thus, adherence to minimal information for studies of extracellular vesicles (MISEV) guidelines is essential to ensure rigor, reproducibility, and transparency. When combined with temporal and cellular specificity, NVU-derived EVs may represent a biomimetic platform for promoting durable recovery in stroke patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Potential of Extracellular Vesicles in Neurovascular Diseases)
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