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>
Subject(s)
Animals , Male , Rats , Blotting, Western , Celecoxib , Cyclooxygenase 2 , Metabolism , Cyclooxygenase 2 Inhibitors , Pharmacology , Disease Models, Animal , Fibrocystic Breast Disease , Metabolism , Hippocampus , Pathology , Immunohistochemistry , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase Kinases , Metabolism , Nitrobenzenes , Pharmacology , Pilocarpine , Proto-Oncogene Proteins c-fos , Metabolism , Pyrazoles , Pharmacology , Rats, Sprague-Dawley , Receptors, GABA-A , Status Epilepticus , Pathology , Sulfonamides , Pharmacology , Synapses , PathologyABSTRACT
Objective To study the proportion of cyclic vomiting syndrome(CVS) developing to migraine by the medium term prognosis,and explore the relationship between CVS and migraine.Methods Twenty-eight of 38 cases who had identified in our clinical records were traced ,each child was matched to a control,and they all conducted a telephone interview by a standardized question.Results Ninteen(46%) of the subject had continued CVS and(or) migraine,the prevalence of past or present migraine in subjects(46%)was significantly higher than that in control group(10.7%)(P=0.003).Conclusion The progonosis of CVS is closely related to migraine,many of the suffers of CVS tend to develop migraine.