| Project/Area Number |
04454365
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Saitama Medical School |
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Principal Investigator |
SHIGENO Taku Saitama Medical School, Associate Professor, 医学部, 助教授 (20170863)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOZAKI Haruhiko Tokyo Metropolitan Institute of Medical Science Director, 部長 (20109945)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Neuronal Death / Glutamate Receptor / Nerve Growth Factor / Endothelin / Hippocampus / グルタミン酸 / 脳虚血 |
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| Research Abstract |
The molecular and neural mechanisms of selective neuronal death have long been discussed. In the hippocampus, CA1 pyramidal cells are known to be vulnerable to ischemia and seizures. At the molecular level, particular attention has been focused on excitotoxicity via glutamate receptors. However, so far the role of glutamate receptors has not been established in the pathogenesis of selective death of CA1 pyramidal cells. We have found that one of the glutamate analogs acting on N-methyl-D-aspartate (NMDA) receptor, the (2S,3R,4S) isomer of alpha- (carboxycyclopropyl) glycine (L-CCG-IV) 1 induces bilateral death of CA1 pyramidal cells when injected into the unilateral CA1 subfield of rats. This phenomenon appears to involve both molecular and neural mechanisms so we have investigated the underlying mechanism by disconnecting the excitatory circuitry between both hemispheres. Here, we report that bisection of the corpus callosum and dorsal hippocampal commissure reduces neuronal death, and abolishes spike discharges and seizure activity. Indirect communications between both hippocampi therefore play a crucial role in mediating seizure and excitotoxic neuronal damage. Although we cannot conclude which pathway is playing a decisive role in mediating seizure and neuronal death, the total absence of seizures by bisection supports the encouraging results of callosotomy for patients with intractable seizure. We further investigated the expression of proteins of NGF families and their receptors after transient cerebral ischemia in rats. We have found that receptor proteins of NGF and BDNF are expressed after ischemia that indicate reparative responses in mitigating ischemic damage. We have also found that endothelin receptor is expressed in ischemic brain. These results may provide a comprehensive aspect of neuronal excitation and brain damage.
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