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

脑血管系统的紊乱可能是老年性痴呆的发病机制之一。神经元对缺血性损伤的反应是不一样的。在海马中，已知短暂性缺血发作可导致Ca 1中神经元的广泛延迟的神经元细胞死亡。我们以前曾报道过，短暂的短暂缺血引起兴奋性丧失，随后是短暂的反弹，扩散的抑郁样电位和突触部位的串珠形成，最后是细胞死亡。目前，我们已经研究了短暂性缺血后发生的形态学和生理学变化的时间依赖性，从雄性大鼠（180- 200 g）制备海马切片（400 μ m）。在乙醚麻醉下，刺激Schaffer侧支通路，从树突层和细胞内记录群体EPAP（pEPSP）。稳定后，用缺乏葡萄糖和氧气（LGO）、具有降低的K和/或具有Ap-5的改良林格溶液灌注切片。将含有使君子酸和NMDA的离子电渗电极定位在树突上。在LGO Ringer、低K（3 mM）LGO和AP-5（5X 10 μ M）LGO Ringer中，在4.5分钟的灌注期间，兴奋性的丧失具有相同的时间过程<-5>。复氧后，低K或AP-5切片的反应几乎恢复到对照组，但仅LGO Ringer切片的反应没有恢复。细胞内记录我们发现，膜电位超极化时的兴奋性的损失，和离子电渗反应增加了很短的时间。我们的结论是，突触传递在缺血的早期阶段被阻断，但递质释放和NMDA受体兴奋引起的损害，导致去极化和死亡。

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.