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Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.11 P.903-915

http://doi.org/10.1631/jzus.B0820018


Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats


Author(s):  Hai-ju ZHANG, Ruo-peng SUN, Ge-fei LEI, Lu YANG, Chun-xi LIU

Affiliation(s):  Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan 430060, China; more

Corresponding email(s):   streeg@sina.com

Key Words:  Epileptogenesis, Cyclooxygenase-2 (COX-2), Neurogenesis, Microglia, &gamma, -amino butyric acid (GABA), c-Fos, Mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK), Spontaneous recurrent seizure


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[J]. Journal of Zhejiang University Science B, 2008, 9(11): 903-915.

@article{title="Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats",
author="Hai-ju ZHANG, Ruo-peng SUN, Ge-fei LEI, Lu YANG, Chun-xi LIU",
journal="Journal of Zhejiang University Science B",
volume="9",
number="11",
pages="903-915",
year="2008",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820018"
}

%0 Journal Article
%T Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats
%A Hai-ju ZHANG
%A Ruo-peng SUN
%A Ge-fei LEI
%A Lu YANG
%A Chun-xi LIU
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 11
%P 903-915
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820018

TY - JOUR
T1 - Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats
A1 - Hai-ju ZHANG
A1 - Ruo-peng SUN
A1 - Ge-fei LEI
A1 - Lu YANG
A1 - Chun-xi LIU
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 11
SP - 903
EP - 915
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820018


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 &gamma;-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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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