Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration

Benjamin M Kidd; Justin A Varholick; Dana M Tuyn; Pradip K Kamat; Zachary D Simon; Lei Liu; Mackenzie P Mekler; Marjory Pompilus; Jodi L Bubenik; Mackenzie L Davenport; Helmut A Carter; Matteo M Grudny; W Brad Barbazuk; Sylvain Doré; Marcelo Febo; Eduardo Candelario-Jalil; Malcolm Maden; Maurice S Swanson

doi:10.1038/s41536-024-00386-8

Stroke-induced neuroplasticity in spiny mice in the absence of tissue regeneration

NPJ Regen Med. 2024 Dec 20;9(1):41. doi: 10.1038/s41536-024-00386-8.

Authors

Benjamin M Kidd^{1

2}, Justin A Varholick³, Dana M Tuyn¹, Pradip K Kamat⁴, Zachary D Simon^{2

5}, Lei Liu², Mackenzie P Mekler¹, Marjory Pompilus⁵, Jodi L Bubenik¹, Mackenzie L Davenport¹, Helmut A Carter¹, Matteo M Grudny^{2

5}, W Brad Barbazuk³, Sylvain Doré^{2

4

5}, Marcelo Febo⁵, Eduardo Candelario-Jalil², Malcolm Maden³, Maurice S Swanson⁶

Affiliations

¹ Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA.
² Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
³ Department of Biology, College of Liberal Arts and Sciences and the Genetics Institute, University of Florida, Gainesville, FL, USA.
⁴ Departments of Anesthesiology, Neurology, Psychology, and Pharmaceutics, Center for Translational Research in Neurodegenerative Disease, and the College of Medicine, University of Florida, Gainesville, FL, USA.
⁵ Department of Psychiatry and the McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
⁶ Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA. [email protected].

Abstract

Stroke is a major cause of disability for adults over 40 years of age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to a severe stroke injury in a highly regenerative adult mammal. Here we investigate the effects of transient ischemia on adult spiny mice, Acomys cahirinus, due to their ability to regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and Acomys showed rapid behavioral recovery post-stroke yet failed to regenerate impacted brain regions. An Acomys brain atlas in combination with functional (f)MRI demonstrated recovery coincides with neuroplasticity. The strength and quality of the global connectome are preserved post-injury with distinct contralateral and ipsilateral brain regions compensating for lost tissue. Thus, we propose Acomys recovers functionally from an ischemic stroke injury not by tissue regeneration but by altering its brain connectome.

Grants and funding

NS048843/U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)