The mechanisms of ischemic neuronal death and its treatment.

在缺血神经元的早期过程中，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纠缠在一起，最终导致不可逆转的神经元损伤。本项目旨在通过不同的方法，从不同的角度对这些病理生理实体进行评估。还展示了保护缺血神经元免受损伤的方法的例子。作为实验模型，细胞和切片的原代培养系统与前脑或局部缺血模型(Hayakawa等)一起新发展起来。作为缺血的早期阶段，谷氨酸的释放和钙的动员以及亚低温对其的抑制作用已被证实(Kataoka等人)。用新合成的肌醇多磷酸研究了细胞内钙离子的释放机理，并对丹曲烯衍生物进行了neu-…研究。更多的防鼠活动(Ozaki和其他人)。作为级联反应，缺血诱导的转录因子AP1结合活性的增强被认为与神经元存活有关(Yoneda等人)。用热休克蛋白或泛素(Kirino等)研究蛋白质代谢障碍和对缺血的特殊合成反应。通过对相关基因的研究和对磷脂的分析(Tamura等人)，提出了与缺血性损伤有关的细胞凋亡机制。在新生动物(冈田等)的神经元中显示了对缺血的特异性抵抗和葡萄糖的重要性。另一方面，在老年动物(Fujishima和其他人)的应激反应中，发现神经元局部脑血流量降低。一种新研制的红细胞变形性分析装置，在自发性高血压大鼠(Uyesaka等人)的红细胞中显示了变形性的增强。较少

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