TAT-Bcl-x(L) improves survival of neuronal precursor cells in the lesioned striatum after focal cerebral ischemia

Cerebral ischemia activates endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus. Consecutively, SVZ-derived neural precursors migrate towards ischemic lesions. However, functional relevance of activated neurogenesis is limited by poor survival of new-born precursors. We th...

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Bibliographic Details
Published in:Neurobiology of disease 2009-04, Vol.34 (1), p.87-94
Main Authors: Doeppner, Thorsten R, Dietz, Gunnar P H, El Aanbouri, Mimount, Gerber, Joachim, Witte, Otto W, Bähr, Mathias, Weise, Jens
Format: Article
Language:English
Subjects:
Animals
bcl-X Protein - therapeutic use
Brain Ischemia - drug therapy
Brain Ischemia - physiopathology
Cell Death - physiology
Cell Survival - physiology
Corpus Striatum - physiopathology
Gene Products, tat - therapeutic use
Learning
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins - metabolism
Motor Activity
Neurogenesis - physiology
Neuropeptides - metabolism
Neuroprotective Agents - therapeutic use
Recombinant Fusion Proteins - therapeutic use
Space Perception
Stem Cells - physiology
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Summary:Cerebral ischemia activates endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus. Consecutively, SVZ-derived neural precursors migrate towards ischemic lesions. However, functional relevance of activated neurogenesis is limited by poor survival of new-born precursors. We therefore employed the HI-virus-derived fusion protein TAT-Bcl-x(L) to study the effects of acute anti-apoptotic treatment on endogenous neurogenesis and functional outcome after transient cerebral ischemia in mice. TAT-Bcl-x(L) treatment led to significantly reduced acute ischemic cell death (128+/-23 vs. 305+/-65 TUNEL+ cells/mm(2) in controls) and infarct volumes resulting in less motor deficits and improved spatial learning. It significantly increased survival of doublecortin (Dcx)-positive neuronal precursors (389+/-96 vs. 213+/-97 Dcx+ cells in controls) but did not enhance overall post-ischemic cell proliferation or lesion-specific neuronal differentiation 28 days after ischemia. Our data demonstrate that post-stroke TAT-Bcl-x(L)-treatment results in acute neuroprotection, improved functional outcome, and enhanced survival of lesion-specific neuronal precursor cells after cerebral ischemia in mice.
ISSN:1095-953X
DOI:10.1016/j.nbd.2008.12.013