Mechanisms of subventricular zone expansion after focal cortical ischemic injury.
The rodent subventricular zone (SVZ) contains neural precursor cells that divide and then die in place or migrate to the olfactory bulb through the rostral migratory stream (RMS) to become new neurons. Despite the normally tight control in cell numbers in this region in adults, previous work from our laboratory and others has shown that SVZ cell number increases after a variety of brain injuries. The relative contribution of changes in rostral migration, cell proliferation, and cell death to increased cell number is poorly understood. We examined these parameters after focal cortical ischemic lesions distal from the SVZ in adult rats. Stereological analysis revealed that cell numbers remain constant in the SVZ and RMS until 5 days postinjury but then rapidly expanded by 150,000 cells by day 7 in each region. Rostral migration of SVZ cells was unaffected by the injury. Both cell death and proliferation increased in the SVZ as early as day 5. However, these two mechanisms became uncoupled when cell number increased, indicating that a distant brain injury expands the SVZ by disrupting the balance between cell death and proliferation in this adult neurogenic zone.
Gotts
Jeffrey E
JE
Department of Neurology, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Chesselet
Marie-Françoise
MF
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine