Department of Radiology, Neuroradiology Division, Stanford University, CA, USA.
Stanford University, Department of Comparative Medicine, Stanford, CA, USA.
Exp Neurol. 2021 Sep;343:113761. doi: 10.1016/j.expneurol.2021.113761. Epub 2021 May 12.
Surgery can be highly effective for treating certain cases of drug resistant epilepsy. The current study tested a novel, non-invasive, surgical strategy for treating seizures in a rat model of temporal lobe epilepsy. The surgical approach uses magnetic resonance-guided, low-intensity focused ultrasound (MRgFUS) in combination with intravenous microbubbles to open the blood-brain barrier (BBB) in a transient and focal manner. During the period of BBB opening, a systemically administered neurotoxin (Quinolinic Acid: QA) that is normally impermeable to the BBB gains access to a targeted area in the brain, destroying neurons where the BBB has been opened. This strategy is termed Precise Intracerebral Non-invasive Guided Surgery (PING). Spontaneous recurrent seizures induced by pilocarpine were monitored behaviorally prior to and after PING or under control conditions. Seizure frequency in untreated animals or animals treated with MRgFUS without QA exhibited expected seizure rate fluctuations frequencies between the monitoring periods. In contrast, animals treated with PING targeting the intermediate-temporal aspect of the hippocampus exhibited substantial reductions in seizure frequency, with convulsive seizures being eliminated entirely in two animals. These findings suggest that PING could provide a useful alternative to invasive surgical interventions for treating drug resistant epilepsy, and perhaps for treating other neurological disorders in which aberrant neural circuitries play a role.
手术对于治疗某些耐药性癫痫病例非常有效。本研究测试了一种新的、非侵入性的手术策略,用于治疗颞叶癫痫大鼠模型中的癫痫发作。该手术方法使用磁共振引导、低强度聚焦超声(MRgFUS)与静脉内微泡相结合,以短暂和局灶的方式打开血脑屏障(BBB)。在 BBB 打开期间,一种系统给予的神经毒素(喹啉酸:QA)通常不能穿透 BBB,从而进入大脑的靶向区域,破坏 BBB 已打开的神经元。这种策略称为精确颅内非侵入性引导手术(PING)。在 PING 或对照条件下,用匹鲁卡品诱导自发性复发性癫痫之前和之后进行行为监测。未治疗的动物或未用 QA 治疗的 MRgFUS 治疗的动物的癫痫发作频率表现出预期的监测期之间的发作率波动频率。相比之下,用 PING 靶向海马体中间颞叶的动物的癫痫发作频率显著降低,有两只动物的惊厥性癫痫完全消除。这些发现表明,PING 可能为治疗耐药性癫痫提供一种有用的替代侵入性手术干预方法,也可能为治疗其他异常神经回路起作用的神经紊乱提供一种方法。