Exp Neurobiol.
2009 Jun;18(1):13-18. 10.5607/en.2009.18.1.13.
Celecoxib Attenuates Kainic Acid-induced Neuronal Cell Death Through Suppression of Microglial c-Jun N-terminal Kinase Phosphorylation
- Affiliations
-
- 1Department of Pharmacology, College of Medicine, Kangwon National University, Chunchon 700-701, Korea. wchun@kangwon.ac.kr
- 2College of Pharmacy, Kangwon National University, Chunchon 700-701, Korea.
- 3Division of Bio-resources Technology, Kangwon National University, Chunchon 700-701, Korea.
- KMID: 2165291
- DOI: http://doi.org/10.5607/en.2009.18.1.13
Abstract
- In the present study, neuroprotective property of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and its underlying mechanism were examined in the animal model of kainic acid (KA)-induced excitotoxicity. KA, administered intracerebroventricularly (i.c.v.), induced marked neuronal cell death with concurrent microglial activation and subsequent induction of inducible nitric oxide synthase (iNOS) in the hippocampus. Histopathological analysis demonstrated that celecoxib (100 mg/kg), pre-treated 1 hr before or post-treated 2 hr after KA i.c.v. injection, significantly attenuated KA-induced death of pyramidal neurons in CA3 region. Celecoxib obviously suppressed KA-induced microglial activation and subsequent iNOS expression. KA- induced phosphorylation of c-Jun N-terminal kinases (JNK) was attenuated with celecoxib treatments. The results of the present study demonstrate that suppression of JNK phosphorylation by celecoxib contributes to its neuroprotective action against KA-induced excitotoxicity suggesting that celecoxib may be a potentially valuable in the treatment of acute brain pathologies associated with excitotoxic neuronal damage such as epilepsy, stroke, and traumatic brain injury.
Keyword
MeSH Terms
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Brain
Brain Injuries
Cell Death
Cyclooxygenase 2
Epilepsy
Hippocampus
JNK Mitogen-Activated Protein Kinases
Kainic Acid
Microglia
Models, Animal
Neurons
Nitric Oxide Synthase Type II
Phosphorylation
Phosphotransferases
Pyrazoles
Stroke
Sulfonamides
Celecoxib
Cyclooxygenase 2
JNK Mitogen-Activated Protein Kinases
Kainic Acid
Nitric Oxide Synthase Type II
Phosphotransferases
Pyrazoles
Sulfonamides
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