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.
Artigo
em Coreano
| WPRIM (Pacífico Ocidental)
| ID: wpr-113454
Biblioteca responsável:
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.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Epilepsia
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Pilocarpina
/
Convulsões
/
Estado Epiléptico
/
Regulação para Cima
/
Western Blotting
/
Morte Celular
/
Apoptose
/
Fibras Musgosas Hipocampais
/
Metaloproteinase 9 da Matriz
/
Metaloproteinases da Matriz
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Coreano
Revista:
Journal of Korean Epilepsy Society
Ano de publicação:
2005
Tipo de documento:
Artigo