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在创伤后癫痫猪模型中进行强大的长期视频脑电图监测。

Robust, long-term video EEG monitoring in a porcine model of post-traumatic epilepsy.

作者信息

Martinez-Ramirez Luis, Slate Andrea, Price George, Duhaime Ann-Christine, Staley Kevin, Costine-Bartell Beth A

机构信息

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Center for Comparative Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

出版信息

eNeuro. 2022 Jun 10;9(4). doi: 10.1523/ENEURO.0025-22.2022.

Abstract

To date, post-traumatic epilepsy (PTE) research in large animal models has been limited. Recent advances in neocortical microscopy have made possible new insights into neocortical PTE. However, it is very difficult to engender convincing neocortical PTE in rodents. Thus, large animal models that develop neocortical PTE may provide useful insights that also can be more comparable to human patients. Because gyrencephalic species have prolonged latent periods, long-term video EEG recording is required. Here, we report a fully subcutaneous EEG implant with synchronized video in freely ambulatory swine for up to 13 months during epileptogenesis following bilateral cortical impact injuries or sham surgery The advantages of this system include the availability of a commercially available system that is simple to install, a low failure rate after surgery for EEG implantation, radiotelemetry that enables continuous monitoring of freely ambulating animals, excellent synchronization to video to EEG, and a robust signal to noise ratio. The disadvantages of this system in this species and age are the accretion of skull bone which entirely embedded a subset of skull screws and EEG electrodes, and the inability to rearrange the EEG electrode array. These disadvantages may be overcome by splicing a subdural electrode strip to the electrode leads so that skull growth is less likely to interfere with long-term signal capture and by placing two implants for a more extensive montage. This commercially available system in this bilateral cortical impact swine model may be useful to a wide range of investigators studying epileptogenesis in PTE.Post-traumatic epilepsy (PTE) is a cause of significant morbidity after traumatic brain injury (TBI) and is often drug-resistant. Robust, informative animal models would greatly facilitate PTE research. Ideally, this biofidelic model of PTE would utilize a species that approximates human brain anatomy, brain size, glial populations, and inflammatory pathways. An ideal model would also incorporate feasible methods for long-term video EEG recording required to quantify seizure activity. Here, we describe the first model of PTE in swine and describe a method for robust long-term video EEG monitoring for up to 13 months post-TBI. The relatively easy "out-of-the-box" radiotelemetry system and surgical techniques described here will be adaptable by a wide array of investigators studying the pathogenesis and treatment of PTE.

摘要

迄今为止,大型动物模型中的创伤后癫痫(PTE)研究一直很有限。新皮质显微镜技术的最新进展为深入了解新皮质PTE提供了可能。然而,在啮齿动物中诱发令人信服的新皮质PTE非常困难。因此,能发展出新皮质PTE的大型动物模型可能会提供有用的见解,也能与人类患者进行更好的对比。由于脑回状物种的潜伏期较长,需要进行长期视频脑电图记录。在此,我们报告一种完全皮下植入的脑电图装置,在自由活动的猪身上,于双侧皮质撞击伤或假手术后的癫痫发生过程中,同步视频记录长达13个月。该系统的优点包括有市售系统可供使用、安装简单、脑电图植入手术后故障率低、无线电遥测能够对自由活动的动物进行连续监测、视频与脑电图同步性极佳以及信噪比高。该系统在这个物种和年龄段的缺点是颅骨生长会完全包埋一部分颅骨螺钉和脑电图电极,并且无法重新排列脑电图电极阵列。通过将硬膜下电极条拼接至电极引线,使颅骨生长不太可能干扰长期信号采集,以及放置两个植入物以获得更广泛的监测组合,可以克服这些缺点。这种在双侧皮质撞击猪模型中使用的市售系统,可能对广泛研究PTE癫痫发生机制的研究人员有用。创伤后癫痫(PTE)是创伤性脑损伤(TBI)后导致显著发病的原因,且常常耐药。强大、信息丰富的动物模型将极大地促进PTE研究。理想情况下,这种PTE的生物逼真模型将采用一种在脑解剖结构、脑大小、神经胶质细胞群和炎症途径方面与人类相近的物种。一个理想的模型还应纳入可行的方法,用于量化癫痫活动所需的长期视频脑电图记录。在此,我们描述了猪身上的首个PTE模型,并描述了一种在TBI后长达13个月进行强大的长期视频脑电图监测的方法。这里描述的相对简单的“开箱即用”无线电遥测系统和手术技术,将可供广泛研究PTE发病机制和治疗方法的研究人员采用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5dc/9275145/bd3aa8048112/ENEURO.0025-22.2022_f001.jpg

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