The mechanisms of ischemic neuronal death and its treatment.

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，进一步进行复杂的细胞内级联反应，与包括神经胶质反应在内的环境变化相互交织，最终导致不可逆的神经元损伤。本项目旨在通过不同的方法从不同的方面对这些病理生理实体进行定位。还展示了保护缺血性神经元免受损伤的方法。作为实验模型，细胞和切片原代培养系统是随着前脑或局部缺血模型而新发展起来的（Hayakawa等）。在缺血的早期阶段，谷氨酸释放和钙动员以及亚低温对其的抑制作用被证实（Kataoka等）。研究了新合成的肌醇多磷酸对细胞内钙离子释放的作用机制；和丹trolene衍生物的新保护活性研究（Ozaki等）。作为级联反应，缺血诱导的转录因子AP1结合活性增强与神经元存活的关系被推测（Yoneda等）。用热休克蛋白或泛素（Kirino等）研究了缺血时蛋白质代谢功能障碍和特殊合成反应。通过对相关基因的研究和磷脂的分析，提出了参与缺血损伤的凋亡机制（Tamura等）。新生动物的神经元显示出对缺血的特异性抵抗和葡萄糖的重要性（Okada等）。另一方面，老年动物的神经元区域脑血流量降低，应激反应升高（Fujishima等）。新近开发了一种分析红细胞变形能力的装置，并在自发性高血压大鼠红细胞中显示出增强的变形能力（Uyesaka等）。少

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