title: Poststroke subgranular and rostral subventricular zone proliferation in a mouse model of neonatal stroke.
abstract: Stroke in the neonatal brain is an understudied cause of neurologic morbidity. Recently we have characterized a new immature mouse model of stroke utilizing unilateral carotid ligation alone to produce infarcts and acute seizures in postnatal day 12 (P12) CD-1 mice. In this study, the amount of poststroke neural progenitor proliferation was examined in the subgranular (SGZ) of the dentate gyrus and the subventricular zone (SVZ) 7, 14, and 21days after ischemia (DAI). A single IP injection (50 mg/kg) of bromodeoxyuridine (BrdU) given 2 hr before perfusion fixation labeled newborn cells. Early cell phenotypes were quantified by colabeling with GFAP, nestin, and DCX. Control mice revealed an age-dependent decrease in neural proliferation, with an approximately 50% drop in BrdU-labeled cell counts at P33 compared with P19 both in the SGZ and in the SVZ. Significant reduction in the amount of neural proliferation in the ipsilateral injured SGZ of ligated mice correlated with both the severity of the stroke-injury and the acute seizure scores. Similar correlations were not detected contralaterally. Contralateral SGZ neural proliferation was initially lowered at 7 DAI but normalized by 21 DAI. In both injured and control brains, approximately 90% of newborn SGZ cells colabeled with nestin, approximately 30% colabeled with GFAP, and a few colabeled with DCX. In contrast, poststroke SVZ cell proliferation was enhanced ipsi- more than contralaterally at 7 DAI. In the SVZ, the enhanced neural proliferation normalized to control levels by P33. In conclusion, the neural cell proliferation was differentially altered in the SGZ vs. SVZ after neonatal stroke.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Kadam
authors.forename: J D
authors.initials: JD
authors.lastname: Mulholland
authors.forename: J W
authors.initials: JW
authors.lastname: McDonald
authors.forename: A M
authors.initials: AM
authors.lastname: Comi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020521:Stroke / Q000503:physiopathology*; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development*
chemical_list: D015415:Biomarkers; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009479:Neuropeptides; D001973:Bromodeoxyuridine