Apoptosis after subarachnoid hemorrhage and its prevention

蛛网膜下腔出血后细胞凋亡及其预防

• 批准号: 11470294
• 负责人: YAMADA Kazuyo
• 金额: $ 9.41万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470294/
• 关键词: apoptosis; subarachnoid hemorrhage; immediate early gene; stress gene; neuron; transporter; intracranial pressure; 低体温; bcl-2

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.

蛛网膜下腔出血（SAH）可引起多种神经功能缺损。其中一些是由脑血管痉挛引起的，但另一些是由SAH的影响引起的。本项目旨在研究对大脑的影响。本实验室建立了大鼠蛛网膜下腔出血模型，并用于原位杂交。结果表明，SAH后24小时内海马CA 1区有促凋亡基因bax和ice表达。凋亡抑制基因bcl-2也在这些区域表达，但bax/bcl-2比值有增高趋势。即早基因、c-fos和c-jun在海马CA 1区表达。监测颅内压时，SAH引起颅内压急剧升高，灌注压持续低5 ~ 15分钟。因此，大脑中发生短暂缺血，最脆弱的CA 1区受到影响。TUNEL染色显示，阳性细胞在CA 1区发作后2天。渗透压通道转运蛋白在CA 1的mRNA表达也增加。这些数据清楚地表明，SAH的应激可能导致神经功能障碍，并可能与SAH引起的神经后遗症有关。

项目成果

Mase M, Yamada K, Iwata A, Matsumoto T, Seiki K, Oda H, Urade Y.: "Acute and transient increase of lipocalin-type prostaglandin D synthase (beta-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage"Neurosci Lett. 270. 18

Mase M、Yamada K、Iwata A、Matsumoto T、Seiki K、Oda H、Urade Y.：“动脉瘤性蛛网膜下腔出血患者脑脊液中脂质运载蛋白型前列腺素 D 合酶（β-痕量）水平的急性和短暂升高”

Katano H, Yamada K, et al.: "Traumatic injury in vitro induces IEG mRNA in cultured glial cells, suppressed by co-culture with neurons"Neuroreport. 10. 2439-2448 (1999)

Katano H、Yamada K 等人：“体外创伤会在培养的神经胶质细胞中诱导 IEG mRNA，并通过与神经元共培养来抑制”Neuroreport。

Aihara N, Yamada K, Komatsu H, Iwata A, Matsumoto T, Nishiho H.: "Temporal pattern of argyrophilic neurons diffuse axonal injury in rats"J Neurotrauma. (in press).

Aihara N、Yamada K、Komatsu H、Iwata A、Matsumoto T、Nishiho H.：“大鼠嗜银神经元弥漫性轴突损伤的时间模式”J Neurotrauma。

Mase M, Yamada K, et al.: "Cerebral Blood flow and merabolism in patients with neuropsychological impirmants after diffuse brain injury. in Chiu W-T(ed)International Conference on Recent Advances in Neurotraumatology"Monduzzi Editore, Bologna, Italy. 351-

Mase M、Yamada K 等人：“弥散性脑损伤后神经心理障碍患者的脑血流和代谢。Chiu W-T（编辑）神经创伤学最新进展国际会议”Monduzzi Editore，意大利博洛尼亚。

Kawamura Y,Yamada K,et al: "Hypothermia modulates induction of hsp70 and c-jun mRNA in the rat brain after subarachnoid hemorrhage"J Neurotrauma. 17(in press). (2000)

Kawamura Y、Yamada K 等人：“低温调节蛛网膜下腔出血后大鼠脑中 hsp70 和 c-jun mRNA 的诱导”J Neurotrauma。