The Role of MMP-9 on the Hippocampal Neuronal Cell Death and Mossy Fiber Sprouting due to Pilocarpine-Induced Status Epilepticus in Mice.
- Author:
Min Kyung CHU
1
;
Yang Je CHO
;
Kyoung Joo CHO
;
Doo Jae LEE
;
Hyun Woo KIM
;
Hyun Jung KIM
;
Gyung Whan KIM
;
Kyoung HEO
;
Byung In LEE
Author Information
1. Department of Neurology and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. bilee@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Seizures;
Gelatinase B;
Apoptosis;
Mossy fiber, hippocampal;
Anthranilic hydroxamic acid
- MeSH:
Adult;
Animals;
Apoptosis;
Blotting, Western;
Caspase 3;
Cell Death*;
DNA Fragmentation;
Extracellular Matrix;
Humans;
Male;
Matrix Metalloproteinase 9;
Matrix Metalloproteinases;
Mice*;
Mossy Fibers, Hippocampal;
Neurons*;
Pilocarpine;
Seizures;
Status Epilepticus*;
Up-Regulation;
Viola
- From:Journal of Korean Epilepsy Society
2005;9(2):119-128
- CountryRepublic of Korea
- Language:Korean
-
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.
