Mechanism for ischemic crosstoleance in central nervous system and its therapeutic application

中枢神经系统缺血交叉耐受机制及其治疗应用

• 批准号: 17390429
• 负责人: SAKABE Takefumi
• 金额: $ 10.28万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390429/
• 关键词: hyperbric oxygen; ischemic tolerance; forebrain ischemia; neurotrophin; immuno; inflammatory response; p38 MAP kinase; クロストレランス; 遺伝子; 耐性関連因子; 中枢神経; 虚血; 耐性誘導

We have previously demonstrated that repeated hyperbaric oxygen (HBO) exposure (3.5 absolute atmosphere (ATA)) prior to ischemia significantly reduced loss of hippocampal CAl neurons after transient forebrain ischemia. The present study examined 1) the effects of different pressure level of HBO, 2) neuroprotective mechanism (by using microarray technology), and 3) biological verification (by using protein synthesis inhibitor).Rats were subjected to forebrain ischemia (8 min)at 12 hours after five sessions of 100% oxygen exposure (100% 02 group) and HBO (at 2 ATA or 3.5 MA, (HBO-2ATA, -3.5ATA group, respectively)) or sham treatment (sham group). 3.5ATA-HBO maximally protected hippocampal CAl neurons (survived neurons : 68%) against ischemic damage(sham group : 2.7%, 100% 02 group : 13.5%, 2 ATA-HBO group : 44%).Microarray data showed significant up-regulation in p75^<NTR>, C/EBP δ, CD74, whose time-course expressions corresponded to HBO-induced neuroprotection. The protein levels were a … More lso significantly increased (2.9, 2.0, and 7.9, respectively). Further, we examined the modulation of neuroprotection by administering protein synthesis inhibitor, anisomycin (AM) or cycloheximide (CY) prior to HBO exposure, both of which inhibited HBO-induced neuroprotection, survived neuron being 2.1 and 8.9% in the rats treated with AM and CY, respectively. With administration of p38 MAP kinase inhibitor, SB203580 (SB), before each treatment with AM-HBO, HBO-induced neuroprotection was resumed. In contrast, with administration of SB before each treatment with CY-HBO, HBO-induced neuroprotection was only marginal. Because AM, but not CY, has been known to have activating property of p38 mitogen-activated protein (p38MAP) kinase, our results suggest that the mechanism of HBO-induced neuroprotection is involved in suppression of p38 MAP kinase.In conclusion, HBO induced neuroprotection against the neuronal damage in the hippocampal CAl following forebrain ischemia is mediated by de novo protein synthesis relevant to neurotrophin and inflammatory-immune system and to suppression of p38 MAP kinase. Less

我们以前已经证明，反复高压氧（HBO）暴露（3.5绝对大气压（ATA））缺血前显著减少海马CA 1神经元短暂前脑缺血后的损失。本研究探讨了1）不同压力水平的高压氧（HBO）对脑缺血再灌注损伤的影响; 2）HBO的神经保护机制（通过使用微阵列技术）和3）生物验证在5次100%氧暴露后12小时，对大鼠进行前脑缺血（8分钟（100%02组）和HBO（2ATA或3.5MA，（分别为HBO-2ATA，-3.5ATA组））或假处理（sham组）。3.5ATA-HBO组海马CA 1区神经元存活率为68%（假手术组为2.7%，100%02组为13.5%，2ATA-HBO组为44%），微阵列显示p75 α<NTR>、C/EBP δ、CD 74表达上调，其表达的时程与HBO的神经保护作用相一致。蛋白质水平是 ...更多信息 LSO显著增加（分别为2.9、2.0和7.9）。此外，我们还研究了蛋白质合成抑制剂茴香霉素（AM）或放线菌酮（CY）在HBO暴露前对神经保护作用的调节作用，这两种药物均抑制HBO诱导的神经保护作用，AM和CY处理的大鼠神经元存活率分别为2.1%和8.9%。在每次AM-HBO治疗前给予p38 MAP激酶抑制剂SB 203580（SB），HBO诱导的神经保护作用恢复。相比之下，在每次CY-HBO治疗前给予SB，HBO诱导的神经保护作用仅为边缘性的。由于已知AM而不是CY具有p38丝裂原活化蛋白（p38 MAP）激酶的激活特性，我们的结果表明HBO诱导的神经保护机制与抑制p38 MAP激酶有关。HBO诱导的对前脑缺血后海马CA 1区神经元损伤的神经保护作用是通过与神经营养因子和炎性因子相关的蛋白质从头合成介导的。免疫系统和抑制p38 MAP激酶。少

项目成果

The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen

• DOI: 10.1016/j.brainres.2006.10.077
• 发表时间: 2007-01-26
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Hirata, Takao;Cui, Ying Jun;Sakabe, Takefumi
• 通讯作者: Sakabe, Takefumi

Ischemic tolerance induced by repeated hyperbaric oxygen In rat brain:Time window and genome-wide gene and protein expression

重复高压氧诱导大鼠脑缺血耐受：时间窗和全基因组基因和蛋白表达

• 发表时间: 2007
• 作者: Takao Hirata;et. al.
• 通讯作者: et. al.

中枢神経における虚血耐性

中枢神经系统的缺血耐受性

• 发表时间: 2005
• 期刊: 蘇生 24
• 作者: 松本 美志也;他;Takao Hirata;山下 敦;松本 美志也
• 通讯作者: 松本 美志也

Ischemic preconditioning in the central nervous system

中枢神经系统缺血预处理

• 发表时间: 2005
• 期刊: Japanese Journal of Reanimatology 24
• 作者: Mishiya;Matsumoto;Kazuhiko;Nakakimura;Mitsuyoshi;Yoshida;Takao;Hirata;Takefumi;Sakabe
• 通讯作者: Sakabe

The temporal profile of genomic responses and protein synthesis in isohemic tolerance of the rat brain induced by repeated hyperbaric oxygen.

重复高压氧诱导的大鼠脑缺血耐受中基因组反应和蛋白质合成的时间曲线。

• 发表时间: 2007
• 期刊: Brain Research 1130
• 作者: 松本 美志也;他;Takao Hirata
• 通讯作者: Takao Hirata