Celecoxib Attenuates Kainic Acid-induced Neuronal Cell Death Through Suppression of Microglial c-Jun N-terminal Kinase Phosphorylation.
- Author:
Jong Seon BYUN
1
;
So Young CHO
;
Song In KIM
;
Yong Soo KWON
;
Seong Ho JEON
;
Myong Jo KIM
;
Hee Jae LEE
;
Sung Soo KIM
;
Wanjoo CHUN
Author Information
- Publication Type:Original Article
- Keywords: kainic acid; celecoxib; cyclooxygenase-2 (COX-2); iNOS; c-Jun N-terminal kinases (JNK); microglia; neuronal death
- MeSH: 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
- From:Experimental Neurobiology 2009;18(1):13-18
- CountryRepublic of Korea
- Language:English
- 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.
