2006 Fiscal Year Final Research Report Summary
Mechanisms of brain edema formation in cerebral contusion: alteration of extra cellular matrix and blood-brain barrier permeability
| Project/Area Number |
16591463
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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 | Nihon University |
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Principal Investigator |
KAWAMATA Tatsuro Nihon University, School of Medicine, Associate Professor, 医学部, 准教授 (20234122)
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| Co-Investigator(Kenkyū-buntansha) |
KATAYAMA Yoichi Nihon University, School of Medicine, Professor, 医学部, 教授 (00125048)
KOSHINAGA Morimichi Nihon University, School of Medicine, Associate Professor, 医学部, 准教授 (30267067)
MORI Tatsuro Nihon University, School of Medicine, Instructor, 医学部, 講師 (00318437)
MAEDA Takeshi Nihon University, School of Dentistry at Matsudo, Instructor, 松戸歯学部, 講師 (70366615)
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| Project Period (FY) |
2004 – 2006
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| Keywords | matrix metalloproteinase / traumatic brain injury / blood-brain barrier / brain edema / cerebral contusion / motor deficit |
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| Research Abstract |
Previous studies have demonstrated that matrix metalloproteinases (MMPs) are upregulated in many pathological conditions such as ischemia, hemorrhage, and trauma in the brain. In the present study, we examined the time course of MMP-9 upregulation, blood-brain barrier (BBB) permeability, brain edema, and motor function following cerebral contusion in rats. MMP upregulation was estimated by gelatin zymography and the BBB integrity was evaluated quantitatively using Evans blue dye. Brain edema was assessed as the brain water content. The Zymograms showed that MMP-9 expression was elevated at 3 hr after injury, reaching a maximum at 18 hr. The peak level of BBB permeability was observed at 6 hr after injury. Brain edema became progressively more severe over time and peaked at 24 hr after injury. Treatment with GM6001, an MMP inhibitor, significantly reduced the BBB permeability at 6 hr (P<0.05) and the brain edema at 24 hr after injury (P<0.05). At 1 and 2 days post-trauma, rats exhibited motor deficits in their rotarod performance, but all recovered by 7 days post-trauma. There were no significant differences in motor deficits between rats treated with or without GM6001. Our findings suggest that MMP-9 contributes to BBB integrity and subsequent brain edema, and MMP inhibitor may have therapeutic effects following traumatic brain injury.
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