TAT-Bcl-x_L improves survival of neuronal precursor cells in the lesioned striatum after focal cerebral ischemia

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• 作者：Thorsten R. Doeppner ; Gunnar P.H. Dietz ; Mimount El Aanbouri ; Joachim Gerber ; Otto W. Witte ; Mathias Bä ; hr ; Jens Weise
• 关键词：Cerebral ischemia ; Endogenous neurogenesis ; Neuroprotection ; TAT fusion proteins
• 刊名：Neurobiology of Disease
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：34
• 期：1
• 页码：87-94
• 全文大小：627 K

文摘

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/mm² 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.