| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
The mechanisms of neuronal death and survival in ischemic brain are one of major topics in neuroscience. Recent papers have stressed the important role of mitochondria in ischemic neuronal damage in that both necrosis and apoptosis are induced by the dysfunction of mitochondria. On the other hand, the induction of ischemic tolerance in neuron after ischemic stress has been reported, but the molecular mechanisms of ischemic tolerance have not been elucidated. In the present study, we used several cerebral ischemic models including a. transient forebrain ischemia in gerbil, b. 3-nitropropionic acid-induced striatal damage in rat, c. permanent middle cerebral artery occlusion in rat, d. transient middle cerebral artery occlusion in rat, e. permanent middle cerebral artery occlusion in mouse in order to examine the relation of mitochondrial function and apoptosis and the mechanism of ischemic tolerance. We have demonstrated that apoptosis was involved in neuronal death in model a and b, that apoptosis related genes and poly(ADP-ribosyl)ation was involved in neuronal damage in model b and c, that thioredoxin is markedly induced in neuron in ischemic penumbra in model c and d, and that chemical preconditioning with 3-nitropropionic acid and overexpression of thioredoxin can induce ischemic tolerance in model a and e.
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