FGF-2-induced cell proliferation stimulates anatomical, neurophysiological and functional recovery from neonatal motor cortex injury.
Infant rats treated with basic fibroblast growth factor-2 (FGF-2) after postnatal day (P)10 motor cortical injury, show functional improvement in adulthood relative to those that do not receive FGF-2. In this study we used a combination of behavioural, immunohistochemical, electrophysiological, electron microscopic and teratological approaches to investigate possible mechanisms by which FGF-2 may influence functional recovery. We show that subcutaneous injections of FGF-2 following bilateral lesions to the motor cortex at P10 in the rat leads to filling of the lesion area with migrating neuroblasts and cycling cells. We assessed the functionality of this tissue in adulthood, and show that cells from the filled region spontaneously fire and form synapses. Behavioural analysis shows enhanced motor performance in the FGF-2-treated lesion rats in comparison to vehicle-treated lesion rats, and this improvement is reversed by removal of the tissue from the previously lesioned area or by blocking cortical regeneration by embryonic treatment with bromodeoxyuridine (BrdU). The results show that FGF-2 stimulates filling of the lesion cavity with cells after neonatal motor cortex lesions, that the new tissue has anatomical and physiological properties similar to control tissue, and that the filled region supports motor behaviour.
Monfils
Marie-H
MH
Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada. monfils@cns.nyu.edu
Driscoll
Ira
I
Kamitakahara
Holly
H
Wilson
Brett
B
Flynn
Corey
C
Teskey
G Campbell
GC
Kleim
Jeffrey A
JA
Kolb
Bryan
B
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000187:drug effects* / Q000254:growth & development / Q000293:injuries; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D016222:Fibroblast Growth Factor 2