丘脑前核电刺激对癫痫猴海马神经递质的影响

Effect of anterior thalamic nuclei stimulation on hippocampal neurotransmitters in monkeys withepilepsy

目的探究对颞叶癫痫猴进行长期、单侧丘脑前核电刺激时，神经递质含量的变化。方法将18只雄性猴分为对照组（6只）、假刺激组（6只）、刺激组（6只）。假刺激组和刺激组动物的丘脑前核均被植入脑深部电刺激系统，并采用海马注射海人酸的方法诱导颞叶癫痫模型。本实验对所有动物采用微透析法及高效液相色谱法提取并测定双侧海马中谷氨酸、1一氨基丁酸和天门冬氨酸的含量。结果注射海人酸后，假刺激组中天门冬氨酸和1一氨基丁酸含量显著增加（P〈0．05），但后期y-氨基丁酸含量逐渐回落至基线。谷氨酸含量在急性期显著下降（P〈0．05），在慢性期逐渐回升。长程丘脑前核电刺激使谷氨酸和天门冬氨酸含量较假刺激组明显下降（P〈0．05），并且维持1一氨基丁酸含量直到实验结束。单侧海马海人酸注射和丘脑前核电刺激并未影响对侧海马神经递质的含量（P〉0．05）。结论神经递质含量主要受同侧半球影响。长程丘脑前核电刺激可以导致癫痫猴海马中神经递质含量朝有利的方向改变，这可能是丘脑前核电刺激在癫痫治疗牛的重要机制。

Objective To explore the changes of neurotransmitter content during long-term, unilateral anterior thalamus stimulation in monkeys with temporal lobe epilepsy. Methods Eighteen male monkeys were divided into a control group, a sham stimulation group, and a stimulation group （n =6 each group）. The anterior thalamic nuclei of the animals in the sham stimulation group and the stimulation group were implanted the deep brain stimulation （DBS） system, and a model of epilepsy was induced by injection of kainic acid in the hippocampus. All the animals in this experiment were extracted by using the microdialysis and high performance liquid chromatography, and the bilateral hippocampal glutamate, y-aminobutyxic acid, and aspartic acid content were measured. Results After injection of kainic acid, the aspartic acid and y-aminobutyric acid content increased significantly in the sham stimulation group （ P 〈 0. 05 ）, but the y-aminobutyric acid content gradually fell to the baseline in the late stage. The glntamic acid content decreased significantly in the acute stage （P 〈 O. 05）, and increased gradually in the chronic stage. Compared with the sham stimulation group, the long-term anterior thalamic nucleus stimulation significantly decreased the glutamic acid and aspartic acid content （P 〈 0. 05）, and maintained the y-aminobutyric acid content until the end of the experiment. The injection of kainic acid in unilateral hippocampus and stimulation of anterior thalamic nucleus did not affect the content of contralateral hippocampus neurotransmitters （P 〉 0. 05）. Conclusions The content of neurotransmitters is mainly affected by the ipsilateral hemisphere. The long-term anterior thalamic nucleus stimulation can cause the content of hippocampus neurotransmitters in epileptic monkey hippocampus changes towards a favorable direction. This may be an important mechanism of anterior thalamic nucleus stimulation in the treatment of epilepsy.