| Project/Area Number |
12671368
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | NAGASKI UNIVERSITY |
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Principal Investigator |
KAMINOGO Makio DEPARTMENT OF NEUROSURGERY, NAGASKI UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (40145256)
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| Co-Investigator(Kenkyū-buntansha) |
松尾 義孝 長崎大学, 医学部・附属病院, 医員
YOSHITAKA Matsuo DEPARTMENT OF NEUROSURGERY, NAGASKI UNIVERSITY, SCHOOL OF MEDICINE, SENIOR RESIDENT
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ISCHEMIC TOLERANCE / FOCAL ISCHEMIA / MATRIX METALOPROTEASE / TIMP-1 / INHIBITOR OF MATRIX METALLOPROTEASE |
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| Research Abstract |
Ischemic tolerance in brain develops when short duration of "sublethal" ischemic insults protect brain tissue from subsequent "lethal" cerebral ischemia. It is considered that the ischemic tolerance is established through activation of intrinsic neuroprotective mechanisms and various kind of pathways are involved in the acquirement of ischemic tolerance.
It has been speculated that activation of matrix metalLoproteases (MMPs) that are the intrinsic metaloprotease, has a role in amelioration of ischemic brain injury. We, therefore, have postulated that activation of TIMP-1 that is an inhibitor of MMPs participates in ischemic tolerance. In the present study, using focal ischemia model of rat (intaluminal middle cerebral artery occlusion (MCA) occlusion method), we investigated the significance of MMPs in development of ischemic brain injury and the role of TIMP-1 in ischemic tolerance.
(1) Cerebral ischemia was induced by 90 min of MGA occlusion. Three days before ischemic insults, 15 min of MCA occlusion was done in four (group A, preconditioning group) and no temporary occlusion was done in four (group B, sham group). The volume of cerebral infraction in group A was 68.6 ± 17.3 mm^3, which was significantly smaller than that in group B (127.6 ± 37.1 mm^3).
(2) TIMP-1 was strongly expressed around cerebral vessels in penumbral area at 2 to 3 days after 15 min of MCA occlusion.
(3) Gelatin zymography indicated that MMP-9 expression was observed in postischemic period and markedly prominent at 2 to 3 days after 90 min of ischemia in group B. In group A, expression was MMP-9 was significantly ameliorated through 6 hours to 7 days after ischemia.
We conclude that these results indicate the involvement of MMP-9 in ischemic brain injury and protective effects of TIMP-1 against it.
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