Yagita Yoshiki, Sakoda Saburo, Kitagawa Kazuo
Department of Neurology, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Brain Nerve. 2008 Nov;60(11):1347-55.
Ischemic stress can induce the expression of selective gene in the brain. In the acute phase of ischemia, immediate early gene is induced, and this is followed by the induction of heat shock proteins, apoptosis-related genes and inflammatory cytokines. Some of the genes expressed in the neuron induce neuronal death while other genes are related to neuronal survival. In the later phase of ischemia, genes related to neurogenesis and tissue remodeling are expressed in the brain. These genes may play an important role in the recovery of neurological function. Many of these genes are expressed mainly in the glial cells in this phase. Ischemic tolerance is powerful protective mechanism phenomenon against ischemic injury. Ischemic tolerance is induced 24-48 hours following sublethal ischemia. Since gene expression is altered during this period, gene expression may be involved in ischemic tolerance. It was reported that induction of favorable gene, such as those for heat shock proteins, might be a molecular mechanism playing some part in ischemic tolerance. On the other hand, DNA microarray analysis reveals that gene suppression, rather than expression, may play an important role in the molecular mechanism underlying ischemic tolerance. Gene expression profiles in ischemic brain and in ischemic tolerance have been investigated and a part of the molecular mechanism involved in those phenomena has been revealed recently. Although further study is necessary, gene expression may be an important therapeutic target in ischemic stroke.
缺血应激可诱导大脑中选择性基因的表达。在缺血急性期,即刻早期基因被诱导表达,随后热休克蛋白、凋亡相关基因和炎性细胞因子也被诱导表达。神经元中表达的一些基因会诱导神经元死亡,而其他基因则与神经元存活有关。在缺血后期,与神经发生和组织重塑相关的基因在大脑中表达。这些基因可能在神经功能恢复中发挥重要作用。在这个阶段,许多此类基因主要在胶质细胞中表达。缺血耐受是针对缺血性损伤的强大保护机制现象。亚致死性缺血后24 - 48小时可诱导缺血耐受。由于在此期间基因表达发生改变,基因表达可能与缺血耐受有关。据报道,诱导有利基因,如热休克蛋白相关基因,可能是缺血耐受分子机制的一部分。另一方面,DNA微阵列分析显示,基因抑制而非基因表达,可能在缺血耐受的分子机制中起重要作用。缺血脑和缺血耐受中的基因表达谱已被研究,并且最近已经揭示了这些现象所涉及的部分分子机制。尽管还需要进一步研究,但基因表达可能是缺血性中风的一个重要治疗靶点。