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The mechanisms of ischemic neuronal death and its treatment.

缺血性神经元死亡的机制及其治疗。

基本信息

批准号：
05305006
负责人：
KATAOKA Kiyoshi
金额：
$ 3.84万
依托单位：
Ehime University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

Following the early process in ischemic neurons, a glutamate surge and a subsequent calcium mobilization, proceed further complicated intracellular cascade reactions, being tangled with environmental changes including glial responses, which eventually lead to irreversible neuronal damage. The present project intended to posturate these patho-physiological entity on different aspects and by different methods. Examples of means to protect ischmic neurons against damage were also demonstrated.As experimental models, primary culture systems of cells and also of slices were newly developed along with forebrain or regional ischemic models (Hayakawa and others). As the very early phase of ischemia, glutamate release and calcium mobilization, and suppressive effects of mild hypothermia thereto were demonstrated (Kataoka and others). Mechanisms of intracellular calcium dischage were studied by newly synthesized inositol polyphosphoric acids ; and dantrolene derivatives were studied on their neu … More roprotective activities (Ozaki and others). As the cascade reactions, an ischemia-induced enhancement of the binding activity of a transcription factor, AP1, was posturated with a speculation of its relation to neuronal survival (Yoneda and others). Dysfunction of protein metabolism and special synthetic response to ischemia were studid by the use of heat shock protein or ubiquitin (Kirino and others). Apoptotic mechanisms were proposed to be involved in ischemic damage through the studies of related genes and analysis of phospholipids (Tamura and others). Specific resistance to ischemia and the importance of glucose were demonstrated in neurons of new born animals (Okada and others). On the other hand, regional cerebral blood flow were found lowered in neurons of aged animals along with elevated stress responses (Fujishima and others). A device for analysis of red cell deformability was newly developed and an enhancement of the deformability was shown in red cells from spontaneously hypertensive rats (Uyesaka and others). Less

在缺血神经元的早期过程之后，谷氨酸激增和随后的钙动员，进行进一步复杂的细胞内级联反应，与包括胶质反应在内的环境变化纠缠在一起，最终导致不可逆的神经元损伤。本课题拟从不同角度、不同方法对这些病理生理实体进行研究。作为实验模型，沿着前脑或局部缺血模型（Hayakawa等），开发了细胞和切片的原代培养系统。作为缺血的极早期阶段，证明了谷氨酸释放和钙动员以及轻度低温对其的抑制作用（Kataoka等）。用新合成的肌醇多磷酸类化合物研究了细胞内钙离子的释放机制，并对丹曲林衍生物的神经功能进行了研究。 ...更多信息保护活动（Ozaki等人）。作为级联反应，缺血诱导的转录因子AP 1的结合活性增强被假定与其与神经元存活的关系有关（Yoneda等）。利用热休克蛋白或泛素（Kirino等）研究了蛋白质代谢功能障碍和对缺血的特殊合成反应。通过对相关基因的研究和磷脂的分析，提出凋亡机制与缺血性损伤有关（Tamura等）。在新生动物的神经元中证明了对缺血的特异性抗性和葡萄糖的重要性（Okada等）。另一方面，发现老年动物的神经元中局部脑血流量降低沿着应激反应升高（Fujishima等人）。新开发了红细胞变形性分析装置，在自发性高血压大鼠（Uyesaka等）的红细胞中显示出变形性增强。少