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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory–motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.

Details

Title
Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory–Motor Cortical Stroke
Author
Livingston, Jessica M 1 ; Lee, Tina T 2 ; Enbar, Tom 3 ; Emerson, Daniele 4   VIAFID ORCID Logo  ; Phillips, Clara M 1 ; Krassikova, Alexandra 2   VIAFID ORCID Logo  ; Bang, K W Annie 5   VIAFID ORCID Logo  ; Kortebi, Ines 4 ; Donville, Brennan W 1 ; Ibragimov, Omadyor S 2 ; Sachewsky, Nadia 1 ; Daniela Lozano Casasbuenas 2   VIAFID ORCID Logo  ; Arman Olfat 2 ; Morshead, Cindi M 6 

 Department of Surgery, Division of Anatomy, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (J.M.L.); [email protected] (E.D.); [email protected] (I.K.); ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada 
 Department of Surgery, Division of Anatomy, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (J.M.L.); [email protected] (E.D.); [email protected] (I.K.); 
 Department of Surgery, Division of Anatomy, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (J.M.L.); [email protected] (E.D.); [email protected] (I.K.); ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Institute of Medical Science, 1 King’s College Circle, University of Toronto, Toronto, ON M5S1A8, Canada 
 Department of Surgery, Division of Anatomy, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (J.M.L.); [email protected] (E.D.); [email protected] (I.K.); ; Institute of Medical Science, 1 King’s College Circle, University of Toronto, Toronto, ON M5S1A8, Canada 
 Lunenfeld-Tanenbaum Research Institute, 600 University Ave., Toronto, ON M5G 1X7, Canada; [email protected] 
 Department of Surgery, Division of Anatomy, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada; [email protected] (J.M.L.); [email protected] (E.D.); [email protected] (I.K.); ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Institute of Medical Science, 1 King’s College Circle, University of Toronto, Toronto, ON M5S1A8, Canada; Institute of Biomedical Engineering, 1 King’s College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada 
First page
663
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
22279059
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2993880947
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.