Krucoff Max O, Zhuang Katie, MacLeod David, Yin Allen, Byun Yoon Woo, Manson Roberto Jose, Turner Dennis A, Oliveira Laura, Lebedev Mikhail A
Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina;
Translational Neural Engineering Lab, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
J Neurophysiol. 2017 Sep 1;118(3):1800-1808. doi: 10.1152/jn.00327.2017. Epub 2017 Jul 12.
Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction. A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60-90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.
脊髓损伤(SCI)或神经系统疾病导致的下肢瘫痪恢复预后不佳,仍是一项巨大的社会负担。神经生理学和神经假体研究有潜力改善这些患者的生活质量;然而,缺乏用于截瘫研究的符合伦理且可持续的非人灵长类动物模型阻碍了该领域的进展。因此,我们的多学科团队开发了一种方法,通过创建一个完全可植入的腰椎硬膜外导管 - 皮下端口系统,在清醒的行为猕猴中诱导暂时瘫痪,该系统能够轻松、可靠地进行靶向药物递送以实现感觉运动阻滞。在跑步机行走过程中,将含有1:200,000肾上腺素的1.5%利多卡因等分试样经皮注入三只恒河猴的端口,同时表面肌电图(EMG)记录它们股四头肌和腓肠肌的肌肉活动。每只动物在注射后60 - 90分钟内实现了EMG幅度减小、自主腿部运动丧失和无法承重,随后功能完全恢复。在瘫痪试验期间,猴子保持警觉且配合,继续获取食物奖励,并且端口在几个月后仍保持功能。这项技术将首次能够在清醒的行为非人灵长类动物截瘫的发作、维持和恢复过程中从皮质和/或脊髓进行记录,从而为回答有关脊髓损伤和恢复的急性神经生理反应的基本神经生理学问题打开大门。对于某些旨在为下肢功能障碍患者开发和测试神经接口解码算法的实验范式,它还将消除永久损伤原本高价值研究动物的必要性。一种新型的可植入腰椎硬膜外导管 - 皮下端口系统能够在清醒的行为非人灵长类动物中进行靶向药物递送并诱导暂时截瘫。三只猕猴在注射含肾上腺素的利多卡因后出现60 - 90分钟的自主腿部运动丧失,随后完全恢复。这项技术首次将能够在截瘫的急性发作、维持和恢复期间从近端中枢神经系统进行符合伦理的实时记录。