Apoptosis after subarachnoid hemorrhage and its prevention

蛛网膜下腔出血（SAH）引起各种类型的神经功能缺损。其中一些是由脑血管痉挛引起的，但也有一些是由SAH的影响引起的。目前的项目旨在研究对大脑的影响。本实验室建立了SAH大鼠模型，并进行了原位杂交。我们发现，在SAH后24小时内，海马CA1中表达了促进凋亡的bax和ice基因。凋亡抑制基因bcl-2在这些区域也有表达，但bax/ bcl-2的比值有升高的趋势。海马CA1区有立即早期基因、c-fos和c-jun的表达。监测颅内压时，SAH引起颅内压急剧升高，灌注压低持续5 ~ 15分钟。因此，脑内发生短暂性缺血，最脆弱的CA1区受到影响。TUNEL染色显示，ictus后2 d CA1区细胞呈阳性。渗透通道转运蛋白在CA1位点的mRNA表达也增加。这些数据清楚地表明，SAH应激可诱发神经功能障碍，并可能与SAH引起的神经系统后遗症有关。

Subarachnoid hemorrhage (SAH) cause various type of neurologic deficits. Some of those are caused by cerebrovascular spasm, but others are caused by impact of SAH. The present project was designed to study the impact to the brain. Rat model of SAH was developed in our laboratory and used for in situ hybridization. We identified that apoptosis promoting bax and ice genes ware expressed in the CA1 of hippocampus within 24 hours after SAH. The bcl-2, apoptosis suppressing gene, was also expressed in those areas, but the ratio of bax/bcls tended to increase. Immediate early gene, c-fos and c-jun are expressed in the CA1 area of hippocampus. When monitoring intracranial pressure, SAH induced steep increase of ICP and perfusion pressure was low for 5- 15 minutes. Therefore, transient ischemia occurred in the brain and most vulnerable CA1 area was affected. TUNEL staining showed positive cells at CA1 area 2 days post ictus. Osmolyte channel transporter was also increased its mRNA expression at CA1. These data clearly demonstrate stress of SAH may induce neurological dysfunction and may relate neurological sequelae caused by SAH.