2010 Fiscal Year Final Research Report
Signaling pathway for acute stage in SAH: protective mechanism with ARB for brain damage
| Project/Area Number |
20591695
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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 | Jichi Medical University |
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Principal Investigator |
KUSAKA Gen Jichi Medical University, 医学部, 講師 (00265258)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Sane 自治医科大学, 医学部, 講師 (70112620)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 脳・神経 / シグナル伝達 / くも膜下出血 / 急性期脳損傷 / 脳血液関門 |
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| Research Abstract |
Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen- activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n_40) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood?brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex., AT1 receptor-bloccker reduced, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. We conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.
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