The Role of MMP-9 on the Hippocampal Neuronal Cell Death and Mossy Fiber Sprouting due to Pilocarpine-Induced Status Epilepticus in Mice / 대한간질학회지
Journal of Korean Epilepsy Society
; : 119-128, 2005.
Article
en Ko
| WPRIM
| ID: wpr-113454
Biblioteca responsable:
WPRO
ABSTRACT
PURPOSE: Matrix metalloproteinases (MMPs) have been known to participate in various pathologic situations by modulating extracellular matrix. Although MMP-9 upregulation has been reported in some experimental seizure models, the exact role of MMP-9 in hippocampal cell death during epileptogenesis and subsequent mossy fiber sprouting (MFS) is not clear. Here, we investigated the role of MMP-9 on hippocampal cell death and MFS after pilocarpine-induced status epilepticus (SE) in mice, using highly specific hydroxamic MMP-9 inhibitor. METHODS: SE was induced by intraperitoneal pilocarpine administration in adult male C57BL/6 mice. MMP-9 specific inhibitor was administered intracerebroventrically 3 h after pilocarpine-induced SE. Expression and activation of MMP-9 were assessed by zymography and Western blot analysis. TdT-mediated UTP-biotin nick end labeling (TUNEL) and caspase-3 activity assay were also performed. MFS was investigated using Timm staining. RESULTS: Increased expression and activation of MMP-9 after pilocarpine-induced SE were observed in zymography and Western blot analysis. MMP-9 specific inhibitor decreased MMP-9 activity in in situ zymography and hippocampal cell death in cresyl violet staining. DNA fragmentation and caspase-3 activity were also attenuated by MMP-9 specific inhibitor. Four months after pilocarpine-induced SE, MFS was evident in vehicle-treated mice; in contrast, MFS was barely observed in MMP-9 specific inhibitor-treated mice. CONCLUSIONS: This study suggests MMP-9 is associated with hippocampal cell death and MFS after pilocarpine-induced SE. Furthermore, the findings that MMP-9 specific inhibitor ameliorates cell death and MFS offers the possibility of MMP-9 specific hydroxamic inhibitor as novel therapeutic strategy to reduce hippocampal damage and epileptogenesis.
Palabras clave
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Pilocarpina
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Convulsiones
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Estado Epiléptico
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Regulación hacia Arriba
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Western Blotting
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Muerte Celular
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Apoptosis
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Fibras Musgosas del Hipocampo
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Metaloproteinasa 9 de la Matriz
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Metaloproteinasas de la Matriz
Límite:
Animals
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Humans
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Male
Idioma:
Ko
Revista:
Journal of Korean Epilepsy Society
Año:
2005
Tipo del documento:
Article