Ford Gregory, Xu Zhenfeng, Gates Alicia, Jiang Ju, Ford Byron D
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 222, Atlanta, GA 30310, USA.
Brain Res. 2006 Feb 3;1071(1):226-36. doi: 10.1016/j.brainres.2005.11.090. Epub 2006 Jan 10.
To gain greater insight on the molecular mechanisms that underlie ischemic stroke, we compared gene expression profiles in transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) stroke models using Expression Analysis Systematic Explorer (EASE) pathway analysis software. Many transcripts were induced in both stroke models, including genes associated with transcriptional pathways, cell death, stress responses and metabolism. However, EASE analysis of the regulated genes indicated molecular functions and biological processes unique to each model. Pathways associated with tMCAO included inflammation, apoptosis and cell cycle, while pMCAO was associated with the induction of genes encoding neurotransmitter receptors, ion channels, growth factors and signaling molecules. An intriguing finding was the involvement of tyrosine kinases and phosphatases following pMCAO. These results provide evidence that neuronal death following tMCAO and pMCAO involves distinct mechanisms. These findings may give new insight to the molecular mechanisms involved in stroke and may lead to novel neuroprotective strategies.
为了更深入地了解缺血性中风的分子机制，我们使用表达分析系统探索者（EASE）通路分析软件，比较了短暂性（tMCAO）和永久性大脑中动脉闭塞（pMCAO）中风模型中的基因表达谱。在这两种中风模型中均诱导了许多转录本，包括与转录途径、细胞死亡、应激反应和代谢相关的基因。然而，对调控基因的EASE分析表明，每个模型都有独特的分子功能和生物学过程。与tMCAO相关的通路包括炎症、凋亡和细胞周期，而pMCAO则与编码神经递质受体、离子通道、生长因子和信号分子的基因诱导有关。一个有趣的发现是pMCAO后酪氨酸激酶和磷酸酶的参与。这些结果提供了证据，表明tMCAO和pMCAO后的神经元死亡涉及不同的机制。这些发现可能为中风涉及的分子机制提供新的见解，并可能导致新的神经保护策略。
