Neuroradiology Section, Department of Radiology, School of Medicine, Stanford University, California, USA.
Neuroradiology Section, Department of Radiology, School of Medicine, Stanford University, California, USA; The Acupuncture and Tuina School/Third Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Ultrasound Med Biol. 2020 May;46(5):1224-1234. doi: 10.1016/j.ultrasmedbio.2020.01.008. Epub 2020 Feb 17.
Surgery to treat drug-resistant epilepsy can be quite effective but remains substantially underutilized. A pilot study was undertaken to test the feasibility of using a non-invasive, non-ablative, approach to produce focal neuronal loss to treat seizures in a rodent model of temporal lobe epilepsy. In this study, spontaneous, recurrent seizures were established in a mouse model of pilocarpine-induced status epilepticus. After post-status epilepticus stabilization, baseline behavioral seizures were monitored for 30 d. Non-invasive opening of the blood-brain barrier targeting the hippocampus was then produced by using magnetic resonance-guided, low-intensity focused ultrasound, through which a neurotoxin (quinolinic acid) administered intraperitoneally gained access to the brain parenchyma to produce focal neuronal loss. Behavioral seizures were then monitored for 30 d after this procedure, and brains were subsequently prepared for histologic analysis of the sites of neuronal loss. The average frequency of behavioral seizures in all animals (n = 11) was reduced by 21.2%. Histologic analyses along the longitudinal axis of the hippocampus revealed that most of the animals (n = 8) exhibited neuronal loss located primarily in the intermediate aspect of the hippocampus, while sparing the septal aspect. Two other animals with damage to the intermediate hippocampus also exhibited prominent bilateral damage to the septal aspect of the hippocampus. A final animal had negligible neuronal loss overall. Notably, the site of neuronal loss along the longitudinal axis of the hippocampus influenced seizure outcomes. Animals that did not have bilateral damage to the septal hippocampus displayed a mean decrease in seizure frequency of 27.7%, while those with bilateral damage to the septal hippocampus actually increased seizure frequency by 18.7%. The animal without neuronal loss exhibited an increase in seizure frequency of 19.6%. The findings indicate an overall decrease in seizure frequency in treated animals. And, the site of neuronal loss along the longitudinal axis of the hippocampus appears to play a key role in reducing seizure activity. These pilot data are promising, and they encourage additional and more comprehensive studies examining the effects of targeted, non-invasive, neuronal lesions for the treatment of epilepsy.
手术治疗耐药性癫痫非常有效，但利用率仍然很低。进行了一项试点研究，以测试使用非侵入性、非消融性方法产生局灶性神经元丧失来治疗颞叶癫痫啮齿动物模型中癫痫发作的可行性。在这项研究中，在匹鲁卡品诱导的癫痫持续状态的小鼠模型中建立了自发性、复发性癫痫。癫痫持续状态后稳定后，监测基础行为性癫痫发作 30 天。然后通过磁共振引导的低强度聚焦超声打开针对海马的血脑屏障，通过该方法将神经毒素（喹啉酸）腹膜内给药进入脑实质，以产生局灶性神经元丧失。在此程序后，然后监测行为性癫痫发作 30 天，随后准备大脑进行神经元丧失部位的组织学分析。所有动物（n=11）的平均行为性癫痫发作频率降低了 21.2%。沿着海马体的纵轴进行组织学分析表明，大多数动物（n=8）表现出主要位于海马体中间部分的神经元丧失，而避开了隔区。另外两只中间海马体受损的动物也表现出明显的双侧隔区损伤。最后一只动物总体上神经元丧失微不足道。值得注意的是，海马体纵轴上神经元丧失的部位影响癫痫发作的结果。没有双侧隔区海马体损伤的动物显示癫痫发作频率平均降低 27.7%，而双侧隔区海马体损伤的动物实际上增加了 18.7%的癫痫发作频率。没有神经元丧失的动物癫痫发作频率增加了 19.6%。这些发现表明治疗动物的癫痫发作频率总体降低。而且，海马体纵轴上神经元丧失的部位似乎在减少癫痫活动方面起着关键作用。这些初步数据很有希望，并鼓励进行更多的和更全面的研究，以检查针对癫痫治疗的靶向、非侵入性、神经元损伤的效果。
