title: Perinatal hypoxia/ischemia damages and depletes progenitors from the mouse subventricular zone.
abstract: Hypoxia-ischemia (H/I) as a result of asphyxia at term remains a major cause of neurologic disability. Our previous studies in the P7 rat model of perinatal H/I have shown that progenitors within the subventricular zone (SVZ) are vulnerable to this insult. Since many investigators are using transgenic and knockout mice to determine the importance of specific molecules in the evolution of damage after a stroke, there is a need to perform comparative studies on the relative vulnerability of the mouse SVZ. Here we assess damage to the SVZ of 5-, 7- and 10-day-old C57BL/6 mice after unilateral common carotid artery cauterization followed by 70 min of H/I (10% O2). Whereas 5- and 7-day-old mice sustained little SVZ damage as assessed by hematoxylin and eosin staining, there was a 16% reduction of cellularity in 10-day-old animals by 18 h of recovery. Additionally, swollen cells were observed in the medial region of the SVZ of 10-day-old mice. However, few caspase-3+ and TUNEL+ cells were observed in this region, which contains the putative neural stem cells. Rather, the majority of the dying cells were situated in the mediolateral and lateral tail of the SVZ. At 18 h of recovery, there was a 2-fold increase in the frequency of TUNEL+ cells in the ipsilateral SVZ as well as a 3-fold increase in the frequency of active-caspase-3+ cells. We conclude that progenitors within the neonatal mouse SVZ are vulnerable to hypoxic/ischemic insult. The demise of these early progenitors likely leads to depletion of neuronal and late oligodendrocyte progenitors, contributing to cerebral dysgenesis.
authors.affiliation: Stem Cell Biology Unit, Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, MD, USA.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Brazel
authors.forename: Robert T
authors.initials: RT
authors.lastname: Rosti
authors.forename: Sheri
authors.initials: S
authors.lastname: Boyce
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Rothstein
authors.forename: Steven W
authors.initials: SW
authors.lastname: Levison
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015984:Causality; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D020547:Lateral Ventricles / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases