Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 903-915, 2008.
Article
in English
| WPRIM
| ID: wpr-359343
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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 alpha-subunit of gamma-amino butyric acid (GABA(A)) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting.</p><p><b>RESULTS</b>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 GABA(A) receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Pilocarpine
/
Pyrazoles
/
Status Epilepticus
/
Sulfonamides
/
Synapses
/
Immunohistochemistry
/
Blotting, Western
/
Proto-Oncogene Proteins c-fos
Limits:
Animals
Language:
English
Journal:
Journal of Zhejiang University. Science. B
Year:
2008
Type:
Article
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