Strauss Kenneth I, Narayan Raj K, Raghupathi Ramesh
Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Neurotox Res. 2004;6(4):333-42. doi: 10.1007/BF03033444.
Cell death/survival following traumatic brain injury (TBI) may be a result of alterations in the intracellular ratio of death and survival factors. Bcl-2 family genes mediate both cell survival and the initiation of cell death. Using lysate RNase protection assays, mRNA expression of the anti-cell death genes Bcl-2 and Bcl-xL, and the pro-cell death gene Bax, was evaluated following experimental brain injuries in adult male Sprague-Dawley rats. Both the lateral fluid-percussion (LFP) and the lateral controlled cortical impact (LCI) models of TBI showed similar patterns of gene expression. Anti-cell death bcl-2 and bcl-xL mRNAs were attenuated early and tended to remain depressed for at least 3 days after injury in the cortex and hippocampus ipsilateral to injury. Pro-cell death bax mRNA was elevated in these areas, usually following the decrease in anti-cell death genes. These common patterns of gene expression suggest an important role for Bcl-2 genes in cell death and survival in the injured brain. Understanding the regulation of these genes may facilitate the development of new therapeutic strategies for a condition that currently has no proven pharmacologic treatments.
创伤性脑损伤（TBI）后的细胞死亡/存活可能是细胞内死亡和存活因子比例改变的结果。Bcl-2家族基因介导细胞存活和细胞死亡的起始。使用裂解物核糖核酸酶保护分析，在成年雄性Sprague-Dawley大鼠实验性脑损伤后，评估抗细胞死亡基因Bcl-2和Bcl-xL以及促细胞死亡基因Bax的mRNA表达。TBI的侧方流体冲击（LFP）模型和侧方控制性皮质撞击（LCI）模型均显示出相似的基因表达模式。抗细胞死亡的bcl-2和bcl-xL mRNA在早期减弱，并且在损伤同侧的皮质和海马中，损伤后至少3天往往仍处于抑制状态。促细胞死亡的bax mRNA在这些区域升高，通常在抗细胞死亡基因减少之后。这些常见的基因表达模式表明Bcl-2基因在受伤大脑的细胞死亡和存活中起重要作用。了解这些基因的调控可能有助于开发针对目前尚无经证实的药物治疗的疾病的新治疗策略。
