Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats.
Recent studies suggest that proliferation in the adult forebrain subventricular zone increases in response to a forebrain stroke and intraventricular infusions of growth factors enhance this response. The potential for growth factor infusions to regenerate the damaged motor cortex and promote recovery of motor function after stroke has not been examined. Here, we report that intraventricular infusions of epidermal growth factor and erythropoietin together, but not individually, promote substantial regeneration of the damaged cerebral cortex and reverse impairments in spontaneous and skilled motor tasks, in a rat model of stroke. Cortical regeneration and functional recovery occurred even when growth factor administration was delayed for up to 7 days after the stroke-induced lesion. Cell tracking demonstrated the contribution of neural precursors originating in the forebrain subventricular zone to the regenerated cortex. Strikingly, removal of the regenerated cortical tissue reversed the growth factor-induced functional recovery. These findings reveal that specific combinations of growth factors can mobilize endogenous adult neural stem cells to promote cortical tissue re-growth and functional recovery after stroke.
Kolb
Bryan
B
Department of Psychology, Canadian Centre for Behavioral Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.
Morshead
Cindi
C
Gonzalez
Claudia
C
Kim
Mina
M
Gregg
Christopher
C
Shingo
Tetsuro
T
Weiss
Samuel
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001973:Bromodeoxyuridine; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D005552:Forelimb / Q000502:physiology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009044:Motor Cortex / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology*; D009068:Movement / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012190:Retroviridae / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*; D013550:Swimming / Q000502:physiology
D000964:Antimetabolites, Antineoplastic; D036341:Intercellular Signaling Peptides and Proteins; D004921:Erythropoietin; D004815:Epidermal Growth Factor; D001973:Bromodeoxyuridine