本文選題：電刺激　切入點：海馬　出處：《浙江大學》2011年博士論文

【摘要】：深部腦刺激是近些年神經(jīng)電生理和神經(jīng)工程領域的研究熱點,特別是海馬神經(jīng)電刺激用于治療或控制癲癇等神經(jīng)疾病的研究越來越受到重視,但是其作用機理仍不明確。由于海馬組織與學習記憶以及許多神經(jīng)疾病相關,因此研究其電刺激的作用機制具有重要意義。 本文利用微刺激電極陣列,對在體大鼠海馬腹側(cè)聯(lián)合(VHC)實施電刺激,并運用記錄位點高密度分布的微電極陣列檢測海馬CA3區(qū)的誘發(fā)群峰電位和神經(jīng)元自發(fā)放電。主要研究了電刺激頻率、強度、刺激持續(xù)時間等參數(shù)變化時,電刺激對于正常和癲癇發(fā)作時大鼠海馬CA3區(qū)神經(jīng)組織的不同作用效果；并且利用海馬CA3區(qū)自發(fā)鋒電位、VHC軸突纖維在刺激前后的發(fā)放變化,以及電刺激對左右兩側(cè)海馬CA3的作用差異,探討了電刺激的作用機理。 本文的主要研究結果如下： (1)高頻電刺激對正常神經(jīng)組織興奮性的影響 本文發(fā)現(xiàn),在神經(jīng)纖維束VHC施加持續(xù)的高頻電刺激可有效抑制其軸突下游所聯(lián)系的遠程神經(jīng)核團CA3的群體興奮性,使得誘發(fā)群峰電位的幅值減小且神經(jīng)元自發(fā)放電減少。該抑制作用與刺激頻率、強度、持續(xù)時間以及刺激電極作用核團之間的距離呈正相關關系。其中達到最大抑制效果的最佳的刺激頻率為125-150 Hz,刺激強度為最大刺激電流的75%,最短刺激持續(xù)時間為30 s。并且該抑制作用效果可逆,一旦停止施加電刺激,誘發(fā)群峰電位的幅值和神經(jīng)元自發(fā)放電活動都會慢慢恢復。 (2)高頻電刺激對癲癇發(fā)作的控制作用 本文結果表明,電刺激能有效降低癲癇發(fā)作的場電位功率,減少癲癇波的發(fā)放,抑制癲癇發(fā)作。此外模擬癲癇發(fā)作間期放電特征的短脈沖串重復刺激同樣有效地降低大鼠CA3區(qū)的場電位功率,抑制癲癇發(fā)作。(3)高頻電刺激的作用機理研究 局部直流電場刺激和軸突復合動作電位實驗的結果表明,高頻電刺激后,神經(jīng)纖維及其下游核團的神經(jīng)元均發(fā)生強烈去極化,從而導致胞外鉀離子濃度升高。鈣調(diào)鉀離子通道的大量開放又可引起超極化后電位作用(AHP),因此本文推測高頻電刺激對神經(jīng)元自發(fā)放電的長效抑制作用很可能與AHP有關。 總之,本文利用在體研究方法,進一步證明了高頻電刺激在抑制癲癇方面的突出表現(xiàn),為癲癇病的臨床治療提供理論依據(jù),對開發(fā)難治性癲癇病的新治療方法具有重要意義。
[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.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R312;R742.1

【引證文獻】

相關博士學位論文 前1條

1 汪洋;大鼠海馬CA1區(qū)神經(jīng)活動對體感刺激響應的研究[D];浙江大學;2014年

相關碩士學位論文 前2條

1 陳白璐;基于寬頻帶記錄信號的神經(jīng)元鋒電位檢測分類新方法及其應用[D];浙江大學;2014年

2 胡振華;實時癲癇電位檢測與閉環(huán)式深部腦刺激系統(tǒng)的設計[D];浙江大學;2014年

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本文編號：1719960