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An animal of senile dementia induced by the damage of the brain vascular system

脑血管系统损伤所致老年痴呆动物

基本信息

批准号：
08557005
负责人：
HORI Nobuaki
金额：
$ 2.24万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557005/
关键词：
vascular systems.beading formation intracellular recordings hippocampus senile dementia delayd neuronal cell death EPSP ischemic damage 脳切片シファーイエロ-電気生理 ATP 老人性痴呆海馬切片 CA1 脳血管障害

项目摘要

One of possible machanisms of senile dementia may be originated by the trouble on the brain vascular systems. Neurons are not equally to ischemic damege. In the hippocampus, it is known that a transient ischemic episode can be result in an extensive delayd neuronal cell death of neurons in Ca1. We have previously reported that brief transient schemia caused loss of excitability, followed by a transient rebound, a spreading depression-like potential and beading formation at synaptic sites and finally cell death. Now we have studied the time-dependence of morphological and physiological changes that occur following transient ischemia, Hippcampal slices (400mum) were prepared from male rats (180-200g). under ether anesthesia and population EPAPs (pEPSP) from the dendrite layr and intracellular recordings were made with stimulation of the Schaffer collateral pathway. After stabilization the slices were perfused with modified Ringer solutions which lacked glucose and oxygen (LGO), had reduced K and/or with Ap-5. An iontophoretic electrode containing quisqualate and NMDA was positioned on the dendrites. The loss of excitability had the same time courses during 4.5 min of perfusion in LGO Ringer, low K (3mM) LGO and AP-5 (5X10^<-5>M) LGO Ringer. Upon reoxygenation, responses from slices with low K or AP-5 recovered almost to control but those only in LGO Ringer did not. With intracellular recording we find membrane potential to be hyperpolarized at the time of loss of excitability, and iontophoretic responses increased for a short time. We conclude that synaptic tranmission is blocked atan early stage of ischemia, but that transmitter release and NMDA receptor excitation causes damage which leads to depolarization and death.

老年性痴呆的发病机制之一可能与脑血管系统的病变有关。神经元对缺血性损伤的反应是不同的。在海马体中，已知短暂性脑缺血发作可导致Ca1神经元广泛延迟的神经元细胞死亡。我们之前曾报道过短暂的暂时性图式导致兴奋性丧失，随后是短暂的反弹、扩散的抑郁样电位和突触部位的束状形成，最后是细胞死亡。为了研究短暂性缺血后形态学和生理变化的时间依赖性，我们制备了雄性大鼠海马切片（400mum）（180-200g）。在刺激Schaffer侧枝通路的情况下，对树突层和细胞内的EPAPs （pEPSP）进行记录。稳定后，将切片灌注缺乏葡萄糖和氧（LGO）、降低K和/或添加Ap-5的改性林格溶液。在树突上放置了含有准质酸和NMDA的离子电泳电极。LGO环区、低K (3mM) LGO环区和AP-5 (5X10^<-5>M) LGO环区在灌注4.5 min时兴奋性丧失的时间相同。再氧化后，低K或AP-5切片的反应几乎恢复到对照水平，而仅在LGO Ringer中的切片则没有。通过胞内记录，我们发现在失去兴奋性时，膜电位呈超极化，离子迁移反应在短时间内增加。我们得出结论，突触传递在缺血早期被阻断，但递质释放和NMDA受体兴奋引起损伤，导致去极化和死亡。