三叉神经电刺激导致海马神经元兴奋性及可塑性改变的丘脑前核机制  

Role of the anterior thalamus nucleus in trigeminal nerve stimulation changing the excitability and plasticity of hippocampal neuron

作　　者：田苗苗[1] 王先红[1] 王玉[1] 

机构地区：[1]安徽医科大学第一附属医院神经内科,安徽合肥230022

出　　处：《中风与神经疾病杂志》2015年第4期307-310,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金资助项目(No.81271444);安徽省战略性新兴产业科技攻关项目(No.11010402168)

摘　　要：目的探讨丘脑前核在三叉神经电刺激(trigeminal nerve stimulation,TNS)治疗匹罗卡品诱导的慢性癫痫大鼠中的作用。方法健康雄性SD大鼠随机分为正常对照(Control)组、模型(Pilo)组、经皮三叉神经电刺激(TNS)组和丘脑前核毁损(anterior thalamus nucleus,ATN)组,其中Pilo组、TNS组、ATN组通过腹腔注射(ip)匹罗卡品(pilocarpine,Pilo)建立慢性癫痫模型,另ATN组采用脑立体定向仪化学毁损丘脑前核,待其切口痊愈后予以上述3组一个月慢性三叉神经电刺激或假性电刺激,最后通过免疫荧光双标测定各组海马内囊泡型GABA转运体(vesicular GABA transporter,VGAT)和囊泡型谷氨酸转运体-1(vesicular glutamate transporter 1,VGLUT1)的表达。结果 (1)TNS组和ATN组在刺激结束后海马VGLUT1整体表达水平呈下降趋势,但TNS组在刺激结束后24 h、72 h较ATN组高(P<0.001,P<0.05),14 d、28 d较ATN组低(P<0.05);(2)VGAT与VGLUT1表达相似,TNS组和ATN组在刺激结束后平均每个细胞VGAT表达量也呈下降趋势。但TNS组在各个时间点表达量均较ATN组高(P<0.05)。结论丘脑前核毁损可能通过降低三叉神经慢性电刺激对大脑皮质、海马神经元的激活,进而影响皮质、海马神经元兴奋性预适应和VGAT和VGLUT1的表达,使其兴奋性阈值得不到增高,最终达到抗癫痫治疗作用。Objective To explore the role of anterior thalamus nucleus in the effect of trigeminal nerve stimulation on the hippocampal expression of VGLUT1 and VGAT. Methods Healthy male SD rats were randomly divided into four groups： Control,Pilo,TNS and ATN group. The rats of Pilo,TNS and ATN group which were introduced status epilepticus by pilocarpine were treated with trigeminal nerve stimulation or sham stimulation for one month after ATN group recovered from anterior thalamus nucleus lesions. The expression of VGLUT1 and VGAT in hippocampus was examined with double immunofluorescence. Results（ 1） The average cell expression level of VGLUT1 in ATN and TNS group rats＇ hippocampus was on the decline post-TNS. The expression of VGLUT1 in TNS group was higher than ATN group at 24 h,72 h（ P 〈0. 001,P〈0. 05）,but lower at 14 d,28 d（ P〈0. 05）.（ 2） The expression of VGAT was similar to VGLUT1. The average cell expression level of VGAT in TNS and ATN group rats＇ hippocampal also showed a trend of decline post-TNS. But the expression of VGAT in TNS group was higher than that of ATN group at all the time points post-TNS（ P〈0. 05）. Conclusion Anterior thalamic nucleus lesions may reduce chronic trigeminal nerve stimulation activating the cortex and hippocampus neuronal,affect these neuronal excitatory preadaptation and the expression of VGLUT1 and VGAT,hinder the raise of excitability threshold,eventually achieve the resistance to the treatment of epilepsy.

关 键 词：癫痫 三叉神经电刺激 囊泡型谷氨酸转运体-1 囊泡型GABA转运体 免疫荧光 

分 类 号：R742.1[医药卫生—神经病学与精神病学]