Abstract: Objective To investigate the effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on electroencephalogram (EEG) and expression of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) in hippocampus of rats with refractory epilepsy (RE), and to explore the possible mechanisms of the therapeutic effect of rTMS on RE. Methods Fifty-four adult male Wistar rats were equally randomized into RE rTMS (rTMS), RE sham-rTMS (srTMS) and normal saline control (NS) groups. RE model was induced by injecting of kainic acid (KA) into the CA3 area of left hippocampus with a stereotaxic apparatus, while NS group was injected by NS. The rats in rTMS group were treated for 10 d (stimulation was given in 5 d and discontinued for 2 d, the whole course was 2 weeks). The expression of BDNF and NPY in hippocampus of rats at 3 weeks after operation were collected for EEG signal analysis before and after rTMS treatment, and compared the spike numbers by using the software running on Matlab 7.0 in different groups. The expression of BDNF and NPY in hippocampus of rats were detected by immunohistochemical technique before and 3 weeks after rTMS treatment. Results After rTMS, the amount of EEG sharp waves was reduced significantly (before rTMS, amount of EEG sharp waves, T3: 16.16 ± 1.17, T4: 14.94 ± 0.98; after rTMS, amount of EEG sharp waves, T3: 9.09 ± 0.67, T4: 8.93 ± 0.91; P = 0.000, for all), and the expression of BDNF, tyrosine protein kinase B (TrkB) and NPY in hippocampus of the rats with RE reduced significantly after low frequency rTMS (before rTMS, BDNF IOD: 49 571.40 ± 2344.02, TrkB IOD: 2946.77 ± 1142.79, NPY IOD: 33 823.05 ± 843.45; after rTMS, BDNF IOD: 29 602.07±1932.82, TrkB IOD: 18 104.34 ± 934.58, NPY IOD: 15 037.14 ± 772.95; P = 0.000, for all). Number of active cell decreased significantly (P = 0.000). Conclusion rTMS can reduce epileptiform discharge and down regulate the expression of BDNF, TrkB and NPY, and thus provides antiepilepsy effect.

Key words: Epilepsy, temporal lobe, Magnetotherapy, Electroencephalography, Nerve tissue proteins, Neuropeptide Y, Disease models, animal

摘要： 目的 研究低频重复经颅磁刺激对难治性颞叶癫痫大鼠的治疗作用，以及对海马脑源性神经营养因子（BDNF）和神经肽Y（NPY）表达水平的影响，以探讨低频重复经颅磁刺激治疗癫痫的可能机制。方法 于海马CA3 区注射海仁酸制备难治性颞叶癫痫大鼠模型，以低频重复经颅磁刺激方法共治疗10 d（连续治疗5 d、间隔2 d，治疗2 周）。分别观察不同处理组大鼠治疗前后海马区脑电图变化及尖波数目；免疫组织化学染色检测手术后第3 周时海马CA3 区BDNF 和NPY 表达变化。结果 与治疗前尖波数目（T3：16.16 ± 1.17，T4：14.94 ± 0.98）比较，低频重复经颅磁刺激治疗后难治性颞叶癫痫大鼠脑电图尖波数目（T3：9.09 ± 0.67，T4：8.93 ± 0.91）明显减少（均P = 0.000）；海马CA3 区BDNF（治疗前后IOD值：49 571.40 ± 2344.02 比29 602.07 ± 1932.82）、酪氨酸蛋白激酶B（TrkB，治疗前后IOD 值：2946.77 ±1142.79 比18 104.34 ± 934.58）和NPY（治疗前后IOD 值：33 823.05 ± 843.45 比15 037.14 ± 772.95）阳性细胞数目明显减少（均P = 0.000）。结论 低频重复经颅磁刺激可以通过降低难治性颞叶癫痫大鼠样放电，以及下调海马BDNF、TrkB 和NPY 表达水平而发挥抗癫痫作用。

关键词: 癫痫, 颞叶, 磁疗法, 脑电描记术, 神经组织蛋白质类, 神经肽Y, 疾病模型, 动物