1997 Fiscal Year Final Research Report Summary
POSSIBLE PARTICIPATION OF NITRIC OXIDE IN THR PATHOGRNESIS UNDERLYING ISCHEMIC CEREBRAL DAMAGE
| Project/Area Number |
07457323
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | SAITAMA MRDICAL SCHOOL |
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Principal Investigator |
MATSUI Toru SAITAMA MEDICAL SCHOOL,FACULTY OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (70199735)
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| Co-Investigator(Kenkyū-buntansha) |
KAIZU Hiroyuki SAITAMA MEDICAL SCHOOL,FACULTY OF MEDICINE, ASSISTANT, 医学部, 助手 (30204308)
MORIMOTO Tadashi SAITAMA MEDICAL SCHOOL,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (20230154)
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| Project Period (FY) |
1997 – 1998
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| Keywords | NITRIC OXIDE / NITRIC OXIDE SYNTHASE / NITRIC OXIDE SYNTHASE INHIBITOR / CEREBRAL ISCHEMIA / PERMANENT ISCHEMIA / TEMPORARY ISCHEMIA / OCCLUSION OF MIDDLE CEREBRAL ARTERY / RATS |
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| Research Abstract |
Although it remains to be yet whether nitric oxide (NO) is neurotoxic or neuroprotective, our recent study elucidated the narrow therapeutic window of LNA,Nw-nitro-L-arginine, against occlusion of the middle cerebral artery in rats (MCAo). Our result was consistent with the report that partial blockade of NO synthase (NOS) was beneficial to the treatment of MCAo in mice. Furthermore, the recent study, using mice genetically deficient in neuronal cNOS,demonstrared that neuronal NO mediated neuronal cell damage due to a focal brain ischemia. Besides these indirect findings, we directly measured the temporal alterations in cerebral NO concentration ([NO]) and NOS activity in rats subjected to permanent and tranaient focal cerebral isehemia and the effects of LNA on both [NO] and ischemic brain damage were examined.
[NO]in the ischemic core increased biphasically at 15-45 min.and at 180-240 min.after MCAo. Restoration of blood flow afler 2 hr of MCAo caused a rapid depression and a subsequent small increase of [NO] at 70-100 min. However, NOS activity of P2 and S2 was at the high level during not only the increasing phase but the decreased phase of [NO]. Administration of LNA in permanent and transient MCAo diminished the changes in [NO] and reduced infarct volume by about 70% at 4 hr post-ischemia.
The phenomenon that [NO] decreased when NOS activity in the ischemic cortex remained at the high level may suggest that overproduced NO may rapidly react with superoxide anion to form peroxynitrite anion. We conclude that these heterogeneous elevations in [NO] are important as to the induction of brain damage due to permanent and transient focal cerebral ischemia.
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