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ZJUS-B
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2008, Vol. 9 Issue (11): 903-915    DOI: 10.1631/jzus.B0820018
Biomedicine     
Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats
Hai-ju ZHANG, Ruo-peng SUN, Ge-fei LEI, Lu YANG, Chun-xi LIU
Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan 430060, China; Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China
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Abstract  Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods: Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABAA) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

Key words： Epileptogenesis      Cyclooxygenase-2 (COX-2)      Neurogenesis      Microglia      γ-amino butyric acid (GABA)      c-Fos      Mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK)      Spontaneous recurrent seizure     
Received: 16 January 2008     
CLC:  R72  
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Hai-ju ZHANG
Ruo-peng SUN
Ge-fei LEI
Lu YANG
Chun-xi LIU
Cite this article:

Hai-ju ZHANG, Ruo-peng SUN, Ge-fei LEI, Lu YANG, Chun-xi LIU. Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2008, 9(11): 903-915.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.B0820018     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2008/V9/I11/903

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