Simulation And Experimental Study On The Neuron Firing Regulated By Picosecond Pulsed Electric Field

Fast-paced,high-pressure modern life,along with aging population,environment deterioration and other social problems,prompts a sharp increase in the number of epileptic,causing great burden to individuals,families and society.Meanwhile,the traditional treatment and neuromodulation therapy of epilepsy can not solve the problems such as the toxic and side effects,risk,and the high cost of treatment,resulting in safe,effective treatment of epilepsy into a bottleneck.Based on this,the treatment method of picosecond pulsed electric field?psPEF?combined with ultra wideband antenna is first proposed by our group.The method can avoid the limitation of existent treatment technology and achieve the purpose of non-invasive,targeted and precise focusing treatment.However,the mechanism of psPEF on cell biological effect is still in the preliminary exploration stage,and the study on deep brain neuron firing regulated by picosecond pulse is still blank.In order to provide more theoretical foundation support and parameter selection basis for the new therapeutic method,the thesis carried out the simulation and experimental study on neuron firing regulated by psPEF.Firstly,based on PSpice and MATLAB software platform,combined with Cartesian transport lattice model and HH model,the 3D circuit model of HH model was established to simulate and analyze the regulatory mechanism of pulsed current/electric field stimulation on neuron firing.The result shows that pulsed electric field stimulation has all the regulation effects of pulsed current stimulation.Compared with pulsed current stimulation,pulsed electric field stimulation has hyperpolarization inhibition.Inhibition mechanism is mainly related to depolarization block or increased the threshold level.Furthermore,considering that the inhibition of neuronal hyperexcitability in the lesion area can be used to treat epilepsy,the 3D circuit model of hippocampal CA1?epileptic focal area?neuron was established by optimizing the 3D HH neuron circuit model,and simulation study on the regulatory mechanism of psPEF stimulation intensity,stimulation pulse width,stimulation frequency,stimulation duration on the hippocampal CA1 neuron bursting was carried out.The result indicates that psPEF can inhibit hippocampal CA1 neuron bursting.The inhibition effect is strongly dependent on the stimulation frequency,and increasing the stimulation duration can significantly improve the inhibition effect.At the same time,the research indicates that the main mechanism of psPEF inhibiting hippocampal CA1 neuron bursting is to block I_NaP.Finally,in vivo animal experiment was carried out to study the regulation effect of psPEF on SD rat hippocampal CA1 neuron spike firing.The result indicates that psPEF can effectively inhibit the hippocampal CA1 neuron spike firing in vivo,and the inhibitory effect is related to both the psPEF stimulation frequency and the stimulation duration.In summary,psPEF can effectively inhibit neuronal excitation,which indicates that psPEF is expected to be used to treat neuronal abnormally excited neuropsychiatric diseases such as epilepsy.The result can lay a certain theoretical and experimental basis for subsequent non-invasive,targeted,and precise focusing treatment of epilepsy using psPEF matched with ultra wideband antenna.