The effects of low frequency repetitive transcranial magnetic stimulation on the rat model of refractory epilepsy and expression of brain-derived neurotrophic factor and neuropeptide Y

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.

DOI:10.3969/j.issn.1672-6731.2011.04.012