摘要
目的 :研究托吡酯对癫大鼠海马区细胞外液氨基酸和神经元凋亡的影响。方法 :采用戊四氮 (PTZ)致模型 ,大鼠癫发作后连续给予托吡酯 (TPM) 80mg·kg-1·d-1和卡马西平 40mg·kg-1·d-1,共 14d。以TUNEL方法标记DNA片段 ,原位检测海马凋亡的神经细胞。脑内微透析技术采集大鼠海马细胞外液 ,反相高效液相色谱技术测定氨基酸类神经递质的含量。结果 :TPM组、卡马西平组与对照组比较 ,凋亡细胞数存在显著差异 (P <0 0 0 1) ,TPM组与卡马西平组相比无显著差异 (P >0 0 5 )。TPM可明显升高海马细胞外液γ 氨基丁酸 (GABA)水平 ,并降低谷氨酸 (Glu)浓度。结论 :TPM可减轻大鼠癫发作后的神经元损伤 ,这种作用可能是氨基酸变化的结果 ;但在我们的实验中 ,没有发现TPM对癫后脑损伤比卡马西平有更明显的神经保护作用。
Aim:To investigate the effects of topiramate on hippocampus extracellular amino acid and neuronal apoptosis in rats by acute seizures.Methods:The rats were treated with topiramate(TPM)at 80 mg·kg -1 ·d -1 or cabamazipine at 40 mg·kg -1 ·d for 2 weeks after PTZ induced seizure.Programmed cell death(Apoptosis)was identified by terminal deoxynucletidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL)assay to detect DNA fragmentation.The extracellular amino acid neurotransmission levels in hippocampus of free-moving rats were detected by microdialysis with HPLC.Results:Administration of topiramate significantly reduced hippocampal neuronal damage.However,no difference in histological study of TUNEL-positive neurons between TPM and cabamazipine groups was found.TPM significantly reduced glutamate level but elevalated GABA levels in the hippocampus of seizure rats.Conclusion:Administration of TPM after experimental status epilepticus can attenuate seizure-induced hippocampal neuronal injury.This effect may,at least in part,be related to the changes of amino acid.However,there was no difference between TPM and cabamazipine histologically.
出处
《中国临床神经科学》
2004年第3期257-260,共4页
Chinese Journal of Clinical Neurosciences
