ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1608615
This article is part of the Research TopicMethods in cellular neurobiology researchView all 5 articles
NMDAR inhibitor preconditioned mesenchymal stromal cell-derived extracellular vesicles enhance post-stroke recovery by targeting excitotoxicity and neuronal regeneration
Provisionally accepted
- 1Hebei University, Baoding, China
- 2First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
- 3Chengde Medical University, Chengde, China
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Stroke remains the leading global cause of disability and mortality. Ischemic stroke triggers NMDAR overactivation, resulting in excitotoxic neuronal injury. Extracellular vesicles (EVs) derived from distinct microenvironmental conditions may exert therapeutic effects in stroke recovery. This study investigated the neuroprotective potential of EV from memantine-preconditioned human umbilical cord mesenchymal stem cells (HUC-MSCs) in stroke models. Following photothrombotic stroke induction in male ICR mice, we intravenously administered memantine-preconditioned HUC-MSC-EVs (M-EV). Behavioral assessments included modified neurological severity scores (mNSS) and Morris water maze tests, while tissue damage was evaluated with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Evans blue extravasation, and immunofluorescence. PCR-array analysis revealed neuronal regeneration pathways activated by M-EV treatment. M-EV demonstrated superior neurorestorative capacity compared to EV, significantly improving functional recovery. miR-139-5p and miR-133b emerged as the predominant miRNAs enriched in M-EV, with their downstream targets showing neuroprotective properties. These miRNA-mediated mechanisms appeared crucial for neural repair processes post-stroke. In oxygen-glucose deprivation (OGD)-challenged HT22 hippocampal neurons, M-EV co-culture enhanced cellular viability, promoted migration, and suppressed apoptosis. The results indicate that memantine preconditioning EVs (or M-EVs) could promote neuroregeneration, offering a translational approach for stroke therapy.
Keywords: extracellular vesicles, ischemic stroke, excitotoxicity, Umbilical cord mesenchymal stem cells, preconditioning, Neuroprotection
Received: 09 Apr 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Zhang, Tian, Bo and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaolu Zhang, Hebei University, Baoding, China
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