Rotenberg Alexander, Muller Paul, Birnbaum Daniel, Harrington Michael, Riviello James J, Pascual-Leone Alvaro, Jensen Frances E
Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue Fegan 9, Boston, MA 02115, USA.
Clin Neurophysiol. 2008 Dec;119(12):2697-702. doi: 10.1016/j.clinph.2008.09.003. Epub 2008 Nov 1.
To test the anticonvulsive potential of a range of repetitive transcranial magnetic stimulation (rTMS) frequencies by novel methods for simultaneous EEG and rTMS in a rat seizure model.
Seizures were triggered by intraperitoneal kainic acid (KA; 10mg/kg). Rats (n=21) were divided into three groups in which individual seizures were treated with rTMS trains at one of three frequencies: 0.25, 0.5 or 0.75 Hz. EEG was continuously viewed by an operator who identified each seizure onset. Consecutive seizures in each animal were (1) treated with active rTMS, (2) treated with sham rTMS, or (3) were untreated. EEG was re-analyzed post hoc by visual inspection, and seizure durations were compared within and between treatment groups.
KA-induced seizures were abbreviated by 0.75 Hz (P=0.019) and 0.5 Hz (P=0.033) active EEG-guided rTMS. In contrast, neither active 0.25 Hz rTMS nor the control conditions affected seizure duration (P>0.2).
We demonstrate that EEG-guided rTMS can suppress seizures in the rat KA epilepsy model, and that the effect is frequency dependent, with 0.75 and 0.5 Hz rTMS being superior to 0.25 Hz rTMS.
These data support the use of rat seizure models in translational research aimed at evaluation and development of effective rTMS anticonvulsive protocols. We also offer a proof of principle that real-time analysis of EEG can be used to guide rTMS to suppress individual seizures.
通过在大鼠癫痫模型中同步进行脑电图(EEG)和重复经颅磁刺激(rTMS)的新方法,测试一系列rTMS频率的抗惊厥潜力。
通过腹腔注射海藻酸(KA;10mg/kg)诱发癫痫发作。将大鼠(n = 21)分为三组,每组分别用三种频率之一的rTMS序列治疗个体发作:0.25、0.5或0.75Hz。由一名操作人员持续观察EEG,确定每次癫痫发作的开始。每只动物的连续发作分别进行如下处理:(1)用活性rTMS治疗,(2)用假rTMS治疗,或(3)不治疗。事后通过目视检查对EEG进行重新分析,并比较治疗组内和组间的癫痫发作持续时间。
0.75Hz(P = 0.019)和0.5Hz(P = 0.033)的活性EEG引导下的rTMS可缩短KA诱导的癫痫发作。相比之下,活性0.25Hz rTMS和对照条件均不影响癫痫发作持续时间(P>0.2)。
我们证明了EEG引导下的rTMS可抑制大鼠KA癫痫模型中的癫痫发作,且该效应具有频率依赖性,0.75Hz和0.5Hz rTMS优于0.25Hz rTMS。
这些数据支持在旨在评估和开发有效的rTMS抗惊厥方案的转化研究中使用大鼠癫痫模型。我们还提供了一个原理证明,即EEG的实时分析可用于引导rTMS抑制个体癫痫发作。