Electrical Stimulation of the Brain for Neural Progenitor Cell Migration

Iwasa, Stephanie N 1, 2 ; Babona-Pilipos, Robart 3 ; Sefton, Elana 1, 2 ;  Popovic, Milos R 1, 2 ; Morshead, Cindi M 1, 3

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3E1, Canada; 2. Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, M4G 3V9, Canada; 3. Department of Surgery, University of Toronto, Toronto, Ontario, M5S 3E1, Canada

Neural stem and progenitor cells (NSPCs) are found in specific regions in the adult brain including the subventricular zone which lines the lateral ventricles.  While these cells are recruited to the damaged area following injury, their innate response is not sufficient for functional recovery. One strategy to improve repair within the brain is through enhancing NSPC migration to the site of injury by galvanotaxis. Galvanotaxis is defined as the migration cells in response to an electric field. Our lab has demonstrated that NSPCs are electro-sensitive cells that migrate rapidly towards the cathode in vitro in the presence of direct current or biphasic, clinically relevant-charge-balanced electrical stimulation.  Here, we investigated whether we could enhance NSPC migration in vivo using a similar electrical stimulation paradigm. Using transgenic mice that ubiquitously express yellow fluorescent protein (YFP) we isolated fluorescent NSPCs and transplanted them onto the corpus callosum of wild-type mice. Platinum wire electrodes were implanted medial and lateral to the transplanted cells with the cathode implanted medially.  Starting at two days post-transplant, brains were stimulated for 3 or 6 days, 3 times/day for 30 minutes (400 Hz, 250 mV/mm). Animals were sacrificed at the end of the stimulation and immunohistochemistry was performed to detect the numbers and location of transplanted YFP cells. Our results show that NSPCs migrate cathodally in vivo in the presence of the applied electric field. Transplanted cells do not differentiate into glial progeny and stimulation does not affect the numbers of immune cells (microglia and macrophages) in the implanted brains. These results demonstrate that electrical stimulation is a promising strategy for promoting NSPC migration to injury sites within the brain.