Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat.
Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and increases in the adult after brain injury. In this study, postnatal day 7 (P7) rats underwent right carotid artery ligation followed by 8% O2 exposure for 90 min, a lesioning protocol that resulted in ipsilateral forebrain hypoxic-ischemic (HI) injury. The effects of HI injury on SVZ cell proliferation and neurogenesis were examined 1-3 wk later by morphometric measurement of dorsolateral SVZ size; by immunoassays to detect incorporation of bromodeoxyuridine (BrdU) in proliferating cells; and by immunoassays of doublecortin, a microtubule-associated protein expressed only by immature neurons. For determining the cell phenotypes of newly generated cells, tissue sections were double labeled with antibodies to BrdU and markers of mature neurons (neuronal nuclear protein), astrocytes (glial fibrillary acidic protein), or oligodendroglia (RIP). HI injury resulted in enlargement of the ipsilateral SVZ at P14-28 and a corresponding increase in BrdU cell numbers both in the ipsilateral SVZ and striatum at P21. HI injury also stimulated SVZ neurogenesis, based on increased doublecortin immunostaining in the SVZ ipsilateral to lesioning at P14-28. However, 4 wk after HI injury, in the lesioned striatum, although BrdU/glial fibrillary acidic protein and BrdU/RIP-labeled cells were identified, no BrdU/neuronal nuclear protein double-labeled cells were found. These results suggest that although acute neonatal HI injury stimulates SVZ proliferation and neurogenesis, there is inadequate trophic support for survival of newly generated neurons. Identification of the trophic factors that enhance maturation and survival of immature neurons could provide important clues for improving recovery after neonatal brain injury.
Ong
Jennifer
J
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Plane
Jennifer M
JM
Parent
Jack M
JM
Silverstein
Faye S
FS
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000473:pathology*; D000089662:Doublecortin Protein; D005260:Female; D005455:Fluorescent Antibody Technique; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D001973:Bromodeoxyuridine