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dc.contributor.authorBaumann, Gisela
dc.contributor.authorTravieso, Lissette
dc.contributor.authorTheus, Michelle H.
dc.contributor.authorLiebl, Daniel J.
dc.date.accessioned2017-02-28T19:06:44Z
dc.date.available2017-02-28T19:06:44Z
dc.date.issued2013-07-04
dc.identifier.urihttp://hdl.handle.net/10919/75196
dc.description.abstractTraumatic brain injury (TBI) elicits identifiable changes within the adult subventricular zone (SVZ). Previously, we demonstrated that EphB3/ephrinB3 interaction inhibits neural stem/progenitor cell (NSPC) proliferation and downregulating this pathway following TBI plays a pivotal role in the expansion of the SVZ neurogenic compartment. It remains unclear, however, what early initiating factors may precede these changes. Using hypoxyprobe-1 (HPb) to identify regions of low oxygen tension or hypoxia (<1%), we found HPb uptake throughout the cortex (CTX), corpus callosum (CC) and SVZ within the first 24 h following controlled cortical impact (CCI) injury. At this early time point, HPb co-localized with EphB3 in the SVZ. NSPC specific markers also co-localized with HPb staining throughout the lateral wall of the ventricle. To determine the cell autonomous effects of hypoxia on EphB3/ephrinB3 signaling in NSPCs, we used an in vitro model of hypoxia to mimic 1% oxygen in the presence and absence of soluble aggregated ephrinB3 (eB3). As expected, hypoxia stimulated the uptake of 5-bromo-2'-deoxyuridine (BrdU) and reduced cell death. Coincident with these proliferative changes, both Hif1-∞ and phospho (p)-AKT were increased while EphB3 expression was decreased. Stimulation of EphB3 attenuated hypoxia-induced proliferation and prevented phosphorylation of AKT. Hif1-∞ accumulation, on the other hand, was not affected by EphB3/ephrinB3 signaling. These findings indicate that this pathway limits the NSPC response to hypoxic stimuli. These studies also suggest that early transient changes in oxygen tension following localized cortical injury may initiate a growth-promoting response in the SVZ.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherSociety for Experimental Biology and Medicineen_US
dc.subjectephrinen_US
dc.subjecthypoxiaen_US
dc.subjectephen_US
dc.subjectsubventricular zoneen_US
dc.subjectAKTen_US
dc.subjectHif1-∞en_US
dc.subjectneural stem/progenitor cellen_US
dc.subjecttraumatic brain injuryen_US
dc.titlePronounced hypoxia in the subventricular zone following traumatic brain injury and the neural stem/progenitor cell responseen_US
dc.typeArticle - Refereeden_US
dc.title.serialExperimental Biology and Medicineen_US
dc.identifier.doihttps://doi.org/10.1177/1535370213494558
dc.identifier.volume238en_US
dc.identifier.issue7en_US
dc.type.dcmitypeTexten_US


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