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 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.
Doeppner
Thorsten R
TR
Department of Neurology, University of Goettingen Medical School, 37075 Goettingen, Germany.
Dietz
Gunnar P H
GP
El Aanbouri
Mimount
M
Gerber
Joachim
J
Witte
Otto W
OW
Bähr
Mathias
M
Weise
Jens
J
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000503:physiopathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015696:Gene Products, tat / Q000627:therapeutic use*; D007858:Learning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity; D055495:Neurogenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013028:Space Perception; D013234:Stem Cells / Q000502:physiology*; D051020:bcl-X Protein / Q000627:therapeutic use*
C494812:Bcl2l1 protein, mouse; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015696:Gene Products, tat; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein