Transcranial Magnetic Stimulation Inhibitive Mechanisms For Pathogenesis Of Epilepsy

Objective: From the view of both neurology and neuroinformatics, on micro- and macro-levels of the neural systems , epilepsy inhibitive mechanisms are investigated via low-frequency repetitive transcranial magnetic stimulation (rTMS).Methods: As temporal lobe epilepsy ( TLE ) is the most common refractory epilepsy in clinic, Lithium-pilocarpine induced TLE of rats is established as a model in this thesis. Three intensities of rTMS with frequency of O.SHz are tested in order to chose the optimal one using the index - Correlation dimension (Dc) of EEG on frontal lobes, temporal lobes and hippocampus of the rat, which is rTMS with 0.4 Telsa, 20 times per day for a week. Since neuron transmitter ( GABA and Glutamate ), c-fos and NGF protein are important on molecular level in pathogenesis mechanisms for TLE, the influence of rTMS is investigated with !H-MRS and immunohistochemical staining methods. The inhibition to neuron apoptosis in hippocampus through rTMS is also explored by TUNEL assay and electron microscope. The neural coding and DC of EEG in hippocampus are estimated. As the electrophysiological inhibitory indexes for TLE seizure, they are principal focus in this research. Results:1. Lithium-pilocarpine induced rats epilepsy model are established and TLE characteristics of this model are verified in symptom, EEG, pathology and iconography.2. Optimal intensity of rTMS ( 0.5Hz, 0.4 Telsa, 20 times per day for a week ) can elevate DC of EEG channels of responsive cortex and hippocampus effectively and show antiepileptic effect.3. 'H-MRS spectra manifest: the relative ratio of NAA/Cr and GABA/Cr significantly increase, Choline/Cr relative ratio markedly decreases in hippocampus of optimal rTMS-treated epilepsy rats.4. Immunohistochemical staining method demonstrates: c-fos protein expression fall off and NGF protein expression augment in hippocampus of rTMS-treated epilepsy rats.5. TUNEL assay indicate that neuronal apoptosis decreased significantly in hippocampus for rTMS-treated chronic TLE groups.6. Ultra structure of hippocampus in rTMS-treated epilepsy rats is improved apparently and edema is alleviated with electron microscope observation.7. To understand electrophysiological inhibitory mechanisms of TLE, how rTMS affects neurons discharge coding pattern in hippocampus is explored. Results show: (1) Average discharge frequency is lowered apparently. (2) Interspike interval(ISI) histogram, diagram of chaotic IS I time series and the first-order return map of ISI series demonstrated that ISI distribution change to normal rats' distribution. (3)The main peak of power intensity function of ISI is around 80Hz and approach to normal rats's. (4)Dc of ISI is no significantly difference with normal rats.Conclusion:Low-frequency rTMS has anticonvulsant effects in many aspects: rTMS has neuroprotective effects against detrimental neuronal transmitters and proteins in pathogenesis of epilepsy. rTMS can inhibit apoptosis and improve the ultrastructure in epileptic focus lesion, which are proven by TUNEL assay and electron microscope. In the view of neuroinformatics, changes in ISI series coding mode and DC of EEG in hippocampus reveal that rTMS affects the neural excitability in the anticonvulsive direction by reducing supersynchronization.