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 possib...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 mlPSCs （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 c^-subunit of y-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.展开更多
Background Glucose transporter 1 defciency syndrome(Glut1DS)was initially reported by De Vivo and colleagues in 1991.This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum.It is a...Background Glucose transporter 1 defciency syndrome(Glut1DS)was initially reported by De Vivo and colleagues in 1991.This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum.It is a treatable neurometabolic condition,where prompt diagnosis and initiation of ketogenic dietary therapy can markedly enhance the prognosis.However,due to its rarity,Glut1DS is susceptible to misdiagnosis or missed diagnosis,which can lead to delayed treatment and irreversible dysfunction of the central nervous system.To promote diagnostic awareness and efective treatments,the recommendations for diagnosis and treatment have been developed.Methods The panel on Glut1DS included 28 participants from the members of the Ketogenic Diet Professional Committee of the Chinese Epilepsy Association and Chinese experts with extensive experience in managing Glut1DS.All authors extensively reviewed the literature,and the survey results were discussed in detail over several online meetings.Following multiple deliberative sessions,all participants approved the fnal manuscript for submission.Results Early diagnosis and timely treatment of Glut1DS are crucial for improving prognosis.Physicians should be alert to suspiction of this disease if the following clinical manifestations appear:seizures,episodic or persistent movement disorders(often triggered by fasting,fatigue,or exercise),delayed motor and cognitive development.Characteristic clinical presentations may include seizures combined with movement disorders,episodic eye-head movements,and paroxysmal exerciseinduced dyskinesia(PED).In these cases,genetic testing should be promptly completed,and a lumbar puncture should be performed if necessary.The ketogenic diet is internationally recognized as the frst-line treatment;the earlier it is started,the better the prognosis.It can efectively control seizures and improve motor disorders.Antiepileptic drug treatment is generally inefective or provides limited symptom improvement before starting the ketogenic diet.Conclusion The recommendations provide clinicians with a relatively systematic guide for the rapid identifcation,diagnosis,and timely treatment of Glut1DS.展开更多
文摘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 mlPSCs （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 c^-subunit of y-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.
基金supported by National Key R&D Program of China(2019YFA0801900).
文摘Background Glucose transporter 1 defciency syndrome(Glut1DS)was initially reported by De Vivo and colleagues in 1991.This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum.It is a treatable neurometabolic condition,where prompt diagnosis and initiation of ketogenic dietary therapy can markedly enhance the prognosis.However,due to its rarity,Glut1DS is susceptible to misdiagnosis or missed diagnosis,which can lead to delayed treatment and irreversible dysfunction of the central nervous system.To promote diagnostic awareness and efective treatments,the recommendations for diagnosis and treatment have been developed.Methods The panel on Glut1DS included 28 participants from the members of the Ketogenic Diet Professional Committee of the Chinese Epilepsy Association and Chinese experts with extensive experience in managing Glut1DS.All authors extensively reviewed the literature,and the survey results were discussed in detail over several online meetings.Following multiple deliberative sessions,all participants approved the fnal manuscript for submission.Results Early diagnosis and timely treatment of Glut1DS are crucial for improving prognosis.Physicians should be alert to suspiction of this disease if the following clinical manifestations appear:seizures,episodic or persistent movement disorders(often triggered by fasting,fatigue,or exercise),delayed motor and cognitive development.Characteristic clinical presentations may include seizures combined with movement disorders,episodic eye-head movements,and paroxysmal exerciseinduced dyskinesia(PED).In these cases,genetic testing should be promptly completed,and a lumbar puncture should be performed if necessary.The ketogenic diet is internationally recognized as the frst-line treatment;the earlier it is started,the better the prognosis.It can efectively control seizures and improve motor disorders.Antiepileptic drug treatment is generally inefective or provides limited symptom improvement before starting the ketogenic diet.Conclusion The recommendations provide clinicians with a relatively systematic guide for the rapid identifcation,diagnosis,and timely treatment of Glut1DS.
