大鼠海马区电刺激抑制癫痫的作用机制研究

发布时间：2018-04-07 16:30

本文选题：电刺激　切入点：海马　出处：《浙江大学》2011年博士论文

【摘要】：深部脑刺激是近些年神经电生理和神经工程领域的研究热点,特别是海马神经电刺激用于治疗或控制癫痫等神经疾病的研究越来越受到重视,但是其作用机理仍不明确。由于海马组织与学习记忆以及许多神经疾病相关,因此研究其电刺激的作用机制具有重要意义。本文利用微刺激电极阵列,对在体大鼠海马腹侧联合(VHC)实施电刺激,并运用记录位点高密度分布的微电极阵列检测海马CA3区的诱发群峰电位和神经元自发放电。主要研究了电刺激频率、强度、刺激持续时间等参数变化时,电刺激对于正常和癫痫发作时大鼠海马CA3区神经组织的不同作用效果；并且利用海马CA3区自发锋电位、VHC轴突纤维在刺激前后的发放变化,以及电刺激对左右两侧海马CA3的作用差异,探讨了电刺激的作用机理。本文的主要研究结果如下： (1)高频电刺激对正常神经组织兴奋性的影响本文发现,在神经纤维束VHC施加持续的高频电刺激可有效抑制其轴突下游所联系的远程神经核团CA3的群体兴奋性,使得诱发群峰电位的幅值减小且神经元自发放电减少。该抑制作用与刺激频率、强度、持续时间以及刺激电极作用核团之间的距离呈正相关关系。其中达到最大抑制效果的最佳的刺激频率为125-150 Hz,刺激强度为最大刺激电流的75%,最短刺激持续时间为30 s。并且该抑制作用效果可逆,一旦停止施加电刺激,诱发群峰电位的幅值和神经元自发放电活动都会慢慢恢复。 (2)高频电刺激对癫痫发作的控制作用本文结果表明,电刺激能有效降低癫痫发作的场电位功率,减少癫痫波的发放,抑制癫痫发作。此外模拟癫痫发作间期放电特征的短脉冲串重复刺激同样有效地降低大鼠CA3区的场电位功率,抑制癫痫发作。(3)高频电刺激的作用机理研究局部直流电场刺激和轴突复合动作电位实验的结果表明,高频电刺激后,神经纤维及其下游核团的神经元均发生强烈去极化,从而导致胞外钾离子浓度升高。钙调钾离子通道的大量开放又可引起超极化后电位作用(AHP),因此本文推测高频电刺激对神经元自发放电的长效抑制作用很可能与AHP有关。总之,本文利用在体研究方法,进一步证明了高频电刺激在抑制癫痫方面的突出表现,为癫痫病的临床治疗提供理论依据,对开发难治性癫痫病的新治疗方法具有重要意义。
[Abstract]:Deep brain stimulation is a hot topic in the field of neurophysiology and neuroengineering in recent years, especially the study of hippocampal nerve stimulation for the treatment or control of epilepsy and other neurological diseases, but its mechanism is still unclear.As hippocampal tissue is associated with learning and memory and many neurological diseases, it is of great significance to study the mechanism of electrical stimulation.In this paper, a microstimulatory electrode array was used to stimulate ventral hippocampal CA3 in rats. The evoked peak potentials and spontaneous discharges of neurons in hippocampal CA3 region were detected by microelectrode array with high density distribution of recording sites.The effects of electrical stimulation on the neural tissue in the CA3 region of the hippocampus of normal and epileptic rats were studied when the frequency, intensity and duration of electrical stimulation were changed.The mechanism of electrical stimulation was discussed by using the changes of spontaneous spike fibers in hippocampal CA3 region before and after stimulation and the difference of effects of electrical stimulation on left and right hippocampal CA3.The main results of this paper are as follows:Effect of high frequency electrical stimulation on excitability of normal nerve tissueIt is found that continuous high frequency electrical stimulation in the nerve fiber bundle VHC can effectively inhibit the population excitability of the remote nerve nucleus CA3 associated with the axon downstream, and decrease the amplitude of the evoked group peak potential and the spontaneous discharge of the neurons.The inhibitory effect was positively correlated with the stimulation frequency, intensity, duration and the distance between the stimulation electrode and the nucleus.The optimal stimulation frequency was 125-150 Hz, the stimulation intensity was 75 with the maximum stimulation current, and the shortest stimulation duration was 30 s.The inhibitory effect is reversible. Once the electric stimulation is stopped, the amplitude of evoked peak potential and the spontaneous discharge activity of neurons will slowly recover.Control effect of high frequency electrical stimulation on epileptic seizuresThe results show that electrical stimulation can effectively reduce the field potential power of epileptic seizures, reduce the release of epileptic waves and inhibit epileptic seizures.In addition, the short pulse string repetitive stimulation which simulates the characteristics of epileptic interictal discharge can also effectively reduce the field potential power in the CA3 region of rats and inhibit the high frequency electrical stimulation of epileptic seizures.The results of local direct current field stimulation and axon compound action potential experiments showed that the neurons of nerve fibers and their downstream nuclei were strongly depolarized after high frequency electrical stimulation, which led to the increase of extracellular potassium ion concentration.The opening of a large number of calmodulating potassium channels can also cause hyperpolarization-induced potential action. Therefore, we speculate that the long-term inhibitory effect of high-frequency electrical stimulation on spontaneous discharges of neurons may be related to AHP.In conclusion, this paper further proves the prominent performance of high frequency electrical stimulation in the suppression of epilepsy, provides theoretical basis for clinical treatment of epilepsy, and is of great significance for the development of a new treatment method for refractory epilepsy.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R312;R742.1

【引证文献】