ORIGINAL RESEARCH article
Front. Stroke
Sec. Acute Stroke and Interventional Therapies
Volume 4 - 2025 | doi: 10.3389/fstro.2025.1602076
This article is part of the Research TopicAstrocytes and Their Crucial Role in Modulating NeurotransmissionView all 5 articles
Astrocyte to Neuron Reprogramming with NeuroD1 for Repair in Canine Stroke
Provisionally accepted
Isaac H Clark*
Zachary Roushdy
Dilmareth Natera-RodriguezKevin SunOlivia Erlanson
Shaimaa Khedr
Walter Low
Andrew Walker Grande- University of Minnesota Twin Cities, St. Paul, United States
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Stroke affects hundreds of thousands of people each year and leads to neuronal damage and often long term disabilities. This study served as an exploratory study investigating astrocyte to neuron reprogramming as a potential treatment for ischemic stroke using a canine model to assess anatomical and functional recovery. The study's exploratory nature involved a small sample size, precluding statistically significant conclusions. For treatment, an adeno associated viral (AAV) vector was constructed such that it would target astrocytes and allow expression of NeuroD1 for the intent of reprogramming them into neurons. Animals were analyzed anatomically using MRI scanning, behaviorally with neurological severity score testing, and cellularly with immunohistochemistry staining. Behaviorally, treated animals recovered more rapidly and to a greater extent than controls; anatomically, treated animals also showed much less ventricle enlargement post stroke; and on the cellular level, treated animals showed a decreased level of astrocyte and microglial activation. These findings suggest that NeuroD1mediated astrocyte reprogramming may reduce neuroinflammation and enhance functional recovery in ischemic stroke, warranting further exploration of this therapeutic approach.
Keywords: Stroke, NeuroD1, astrocycte, canine, AAV (Adeno-associated vector)
Received: 28 Mar 2025; Accepted: 05 Jun 2025.
Copyright: © 2025 Clark, Roushdy, Natera-Rodriguez, Sun, Erlanson, Khedr, Low and Grande. 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: Isaac H Clark, University of Minnesota Twin Cities, St. Paul, United States
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