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생쥐 Pilocarpine 모델에서 중첩경련으로 유발한 해마신경세포 사멸과 이끼섬유발아에 대한 MMP-9의 역할

Other Titles
 The Role of MMP-9 on the Hippocampal Neuronal Cell Death and Mossy Fiber Sprouting due to Pilocarpine-Induced Status Epilepticus in Mice 
 주민경  ;  조양제  ;  이병인  ;  허경  ;  김경환  ;  김현정  ;  김현우  ;  이두재  ;  조경주 
 Journal of Korean Epilepsy Society (대한간질학회지), Vol.9(2) : 119-128, 2005 
Journal Title
 Journal of Korean Epilepsy Society (대한간질학회지) 
Issue Date
Seizures ; Gelatinase B ; Apoptosis ; mossy fiber ; hippocampal ; anthranilic hydroxamic acid
Seizures ; Gelatinase B ; Apoptosis ; mossy fiber ; hippocampal ; anthranilic hydroxamic acid
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.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
Kim, Hyun Woo(김현우)
Lee, Byung In(이병인)
Cho, Kyuong Joo(조경주)
Cho, Yang Je(조양제)
Chu, Min Kyung(주민경) ORCID logo https://orcid.org/0000-0001-6221-1346
Heo, Kyoung(허경)
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