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Exp Neurol. 2010 Jun;223(2):548-56. doi: 10.1016/j.expneurol.2010.02.001. Epub 2010 Feb 12.

Protection of hippocampal neurogenesis by TAT-Bcl-x(L) after cerebral ischemia in mice.

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  • 1Department of Neurology, University of Goettingen Medical School, Robert-Koch-Str. 40, 37075 Goettingen, Germany. thorsten.doeppner@medizin.uni-goettingen.de

Abstract

Endogenous neurogenesis persists in the subgranular zone (SGZ) of the adult rodent brain. Cerebral ischemia stimulates endogenous neurogenesis involving proliferation, migration and differentiation of SGZ-derived neural precursor cells (NPC). However, the biological meaning of this phenomenon is limited by poor survival of NPC. In order to study the effects of an acute neuroprotective treatment on hippocampal endogenous neurogenesis after transient cerebral ischemia in mice, we applied a fusion protein consisting of the TAT domain of the HI virus with the anti-apoptotic Bcl-x(L). Intravenous injection of TAT-Bcl-x(L) resulted in reduced hippocampal cell injury for up to 4weeks after stroke as assessed by TUNEL and NeuN staining. This was in line with a TAT-Bcl-x(L)-mediated reduced postischemic microglia activation. Analysis of endogenous hippocampal cell proliferation revealed an increased number of BrdU(+) cells in the TAT-Bcl-x(L) group 4weeks after stroke compared to animals treated with saline and TAT-HA (negative control). Cell proliferation in non-ischemic sham operated animals was not affected by TAT-Bcl-x(L). Twenty-eight days after stroke co-expression of BrdU(+) cells with the immature neuronal marker doublecortin was significantly increased in TAT-Bcl-x(L) animals. Although TAT-Bcl-x(L) treatment also resulted in an increased number of BrdU(+) cells expressing the mature neuronal marker NeuN, the total amount of these cells was low. These data show that TAT-Bcl-x(L) treatment yields both postischemic sustained hippocampal neuroprotection and increased survival of NPC rather than an induction of endogenous neurogenesis itself.

Copyright (c) 2009 Elsevier Inc. All rights reserved.

PMID:
20156439
[PubMed - indexed for MEDLINE]
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