Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 2, March-April, p. 317–325
Publication type: original article
The Effects of Repetitive Transcranial Magnetic Stimulation on Picrotoxin-Induced Convulsions in Mice
1 Department of Neurology and Neurosurgery, Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus
2 Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus
3 Department of Pharmacology, Belarusian State Medical University, Minsk, Belarus
4 Institute of Physiology, National Academy of Sciences of Belarus, Minsk, Belarus
Background. Clinical and experimental results show that repetitive transcranial magnetic stimulation (rTMS) is effective and safe in the treatment of epilepsy. The characteristics of the impulse magnetic field (IMF) are empirical in these studies, making impossible to compare their effectiveness.
Objectives. The article presents the results of a study of the anticonvulsive effects of different modes of IMF on the picrotoxin seizure model, which is important for studying GABAergic brain mechanisms activated by rTMS.
Material and Methods. The experiments were performed on outbred male mice (n = 597; 450 in the experimental group and 147 in the control group). The picrotoxin was injected in a dose of 2.5 mg/kg subcutaneously after either rTMS or a placebo. The rTMS regimes varied in frequency (0.1, 0.3, 0.5, 1.0 and 10 Hz), intensity (10, 20 and 40% of maximal magnetic induction [MMI] of the big ring coil) and the number of procedures (1, 3, 10). The dependence of the criterial characteristics on the TMS parameters was shown in this convulsive model.
Results. The analysis of the data obtained showed that 10 rTMS sessions at an intensity of 20% of MMI in the range of frequencies from 0.5 to 1.0 Hz had the most stable and significant effect in terms of reducing the convulsive readiness of the brain, evaluated by the latent period of the myoclonuses in the picrotoxin test. In all the regimes of exposure, rTMS decreased the number of seizures in the picrotoxin model by 1.5–2 points; the most significant effect was obtained with 10 rTMS sessions in the 0.5–1.0 Hz frequency range and an intensity of 20% of the MMI (р < 0.01).
Conclusion. The study results support the use of IMF as therapy for blocking convulsive attacks.
repetitive transcranial magnetic stimulation, anticonvulsive effect, picrotoxin convulsions model
- Fitzgerald PB, Brown TL, Daskalakis ZJ: The application of transcranial magnetic stimulation in psychiatry and neuroscience’s research. J Acta Psychiatr Scand 2002, 105, 324–340.
- Rossi S, Hallett M, Rossini PM, Pascual-Leone A: Safety of TMS Consensus Group. Clin Neurophysiol 2009, 120, 2008–2039.
- Bae EH, Schrader LM, Machiiet K, Alonso-Alonso M, Riviello Jr JJ, Pascual-Leone A: Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: A review of the literature. Epilepsy Behav 2007, 10, 521–528.
- Chen R, Wassermann EM, Hallet M: Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 1997, 48, 1398–1403.
- Funke K, Benali A: Modulation of cortical inhibition by rTMS – findings obtained from animal models. J Physiol 2011, 589, 4423–4435.
- Theodore WH: Transcranial magnetic stimulation in epilepsy. Epilepsy Curr 2003, 3, 191–197.
- Zhang JQ, Yu JM, Wang XM, Zhao HN, Huang M, Zhang XD: Effects of pretreatment with low-frequency repetitive transcranial magnetic stimulation on expressions of hippocampus GAD65 and NMDAR-1 in rats with pilocarpine-induced seizures. Chin J Neuroimmunology and Neurology 2008, 15, 430–433.
- Cantello R, Rossi S, Varassi C, Ulivelli M, Civardi C, Bartalini S: Slow repetitive TMS for drug-resistant epilepsy: Clinical and EEG findings of a placebo-controlled trial. Epilepsia 2007, 48, 366–374.
- Fregni F, Otachi PT, Do Valle A: A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol 2006, 60, 447–455.
- Rotenberg A, Bae EH, Takeoka M: Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua. Epilepsy Behav 2009, 14, 253–257.
- Rotenberg A, Depositario-Cabacar D, Bae EH, Harini C, Pascual-Leone A, Takeoka M: Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen’s encephalitis. Epilepsy Behav 2008, 13, 260–262.
- Sun W, Mao W, Meng X, Wang D, Qiao L, Tao W: Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy. Clin EEG and Neurosci 2011, 42, 40–44.
- Fregni F, Thome-Souza S, Bermpohl F: Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: An EEG and clinical study. Stereotact Funct Neurosurg 2005, 83, 57–62.
- Hsu WY, Cheng CH, Lin M-W, Shih YH, Liao KK, Lin YY: Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis. Epilepsy Res 2011, 96, 231–240.
- Akamatsu N, Fueta Y, Endo Y, Matsunaga K, Uozumi T, Tsuji S: Decreased susceptibility to pentylenetetrazolinduced seizures after low-frequency transcranial magnetic stimulation in rats. Neurosci Lett 2001, 310, 153–156.
- Anschel DJ, Pascual-Leone A, Holms GL: Anti-kindling effect of slow repetitive transcranial magnetic stimulation in rats. Neurosci Lett 2003, 351, 9–12.
- Godlevsky LS, Kobolev EV, Egidius van L: Influence of transcranial magnetic stimulation on spike–wave discharges in a genetic model of absence epilepsy. Indian J Exp Biol 2006, 44, 949–954.
- Huang M, Yu JM, Wang XM, Wang L: The effects of pretreatment with low frequency transcranial magnetic stimulation on rats with pilocarpine-induced seizures. Chin J Phys Med Rehabil 2009, 3, 228–231.
- Rotenberg A, Muller P, Birnbaum D, Harrinqton M, Riviello JJ, Pascual-leone A, Jensen FE: Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat. Clin Neurophysiol 2008, 119, 2697–2702.
- Kammer T, Beck S, Thielscher A, Laubis-Herrmann U, Topka H: Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types. Clin Neurophysiol 2001, 12, 250–258.
- Newland CF, Cull-Candy SG: On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat. J Physiol 1992, 447, 191–213.
- Todd G, Flavel SC, Ridding MC: Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans. J Appl Physiol 2006, 101, 500–505.
- Fitzgerald PB, Fountain S, Daskalakis ZJ: A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol 2006, 117, 2584–2596.
- Freund TF: GABAergic septal and serotonergic median raphe afferents preferentially innervate inhibitory interneurons in the hippocampus and dentate gyrus. Epilepsy Res 1992, 7, 79–91.
- Freund TF: Interneuron diversity series: Rhythm and mood in perisomatic inhibition. Trends Neurosci 2003, 28, 489–495.
- Funke K, Benali A: Cortical cellular actions of transcranial magnetic stimulation. Restor Neurol Neurosci 2010, 28, 399–417.
- Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C: Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 2004, 5, 793–807.
- Benali A, Trippe J, Weiler E, Mix A, Petrasch-Parwez E, Girzalsky W, Eysel UT, Erdmann R, Funke K: Thetaburst transcranial magnetic stimulation alters cortical inhibition. J Neurosci 2011, 31, 1193–1203.