| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
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.
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