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腹侧苍白球深部脑刺激可减轻毛果芸香碱处理大鼠的癫痫样活动和惊厥行为。

Deep Brain Stimulation of the Ventral Pallidum Attenuates Epileptiform Activity and Seizing Behavior in Pilocarpine-Treated Rats.

作者信息

Yu Wilson, Walling Ian, Smith Autumn B, Ramirez-Zamora Adolfo, Pilitsis Julie G, Shin Damian S

机构信息

Center for Neuropharmacology & Neuroscience, Albany Medical College, Albany, NY, USA.

Department of Neurology, Albany Medical Center, Albany, NY, USA.

出版信息

Brain Stimul. 2016 Mar-Apr;9(2):285-95. doi: 10.1016/j.brs.2015.11.006. Epub 2015 Nov 26.

DOI:10.1016/j.brs.2015.11.006
PMID:26723019
Abstract

BACKGROUND

Brain stimulation is effective for people with intractable epilepsy. However, modulating neural targets that provide greater efficacy to more individuals is still needed.

OBJECTIVE/HYPOTHESIS: We investigate whether bilateral deep brain stimulation of the ventral pallidum (VP-DBS) has potent seizure control in pilocarpine-treated rats.

METHODS

VP-DBS (50 Hz) was applied prior to generalized forebrain seizures or after generalized brainstem seizures manifested. Behavioral seizures were assessed using a modified Racine scale. In vitro and in vivo electrophysiological techniques were employed to identify how VP-DBS affects proximal and distal neuronal activity. The open field test was used to see if acute and chronic VP-DBS affected gross motor function or arousal state. Parametric and non-parametric statistics with post-hoc analysis were performed.

RESULTS

VP-DBS prior to pilocarpine prevented behavioral forebrain and brainstem seizures in most animals (n = 15). VP-DBS after brainstem seizures emerged prevented or reduced the appearance of subsequent behavioral brainstem seizures (n = 11). VP-DBS attenuated epileptiform activity in the hippocampus (n = 5), but not in the primary somatosensory cortex (S1) (n = 4) in vivo. Electrical stimulation in the VP increased VP GABAergic neuronal firing activity from 3.1 ± 1.4 Hz to 7.6 ± 1.7 Hz (n = 8) in vitro and reduced substantia nigra reticulata and superior colliculus neuronal spiking activity from 25.4 ± 3.3 Hz to 18.2 ± 1.4 Hz (n = 6) and 18.2 ± 1.4 Hz to 11.0 ± 1.1 Hz (n = 18), respectively, in vivo.

CONCLUSION

VP-DBS can be a novel and potent therapeutic approach for individuals with intractable epilepsy.

摘要

背景

脑刺激对难治性癫痫患者有效。然而,仍需要调节能为更多个体带来更高疗效的神经靶点。

目的/假设:我们研究双侧苍白球腹侧深部脑刺激(VP-DBS)对毛果芸香碱处理的大鼠是否具有有效的癫痫控制作用。

方法

在全身性前脑癫痫发作之前或全身性脑干癫痫发作出现之后施加VP-DBS(50赫兹)。使用改良的拉辛量表评估行为性癫痫发作。采用体外和体内电生理技术来确定VP-DBS如何影响近端和远端神经元活动。使用旷场试验来观察急性和慢性VP-DBS是否影响总体运动功能或觉醒状态。进行了参数和非参数统计以及事后分析。

结果

在毛果芸香碱处理之前进行VP-DBS可预防大多数动物(n = 15)的行为性前脑和脑干癫痫发作。脑干癫痫发作出现后进行VP-DBS可预防或减少随后行为性脑干癫痫发作的出现(n = 11)。VP-DBS减弱了体内海马体中的癫痫样活动(n = 5),但在初级体感皮层(S1)中未减弱(n = 4)。体外实验中,VP内的电刺激使VP内γ-氨基丁酸能神经元的放电活动从3.1±1.4赫兹增加到7.6±1.7赫兹(n = 8),体内实验中,分别使黑质网状部和上丘神经元的放电活动从25.4±3.3赫兹降低到18.2±1.4赫兹(n = 6)以及从18.2±1.4赫兹降低到11.0±1.1赫兹(n = 18)。

结论

VP-DBS可能是一种针对难治性癫痫患者的新型有效治疗方法。

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