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A novel paraplegia model in awake behaving macaques.

Publication ,  Journal Article
Krucoff, MO; Zhuang, K; MacLeod, D; Yin, A; Byun, YW; Manson, RJ; Turner, DA; Oliveira, L; Lebedev, MA
Published in: J Neurophysiol
September 1, 2017

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.NEW & NOTEWORTHY 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.

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Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

September 1, 2017

Volume

118

Issue

3

Start / End Page

1800 / 1808

Location

United States

Related Subject Headings

  • Walking
  • Wakefulness
  • Spinal Cord Injuries
  • Paraplegia
  • Neurology & Neurosurgery
  • Neurological Rehabilitation
  • Muscle, Skeletal
  • Muscle Contraction
  • Male
  • Macaca mulatta
 

Citation

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Krucoff, M. O., Zhuang, K., MacLeod, D., Yin, A., Byun, Y. W., Manson, R. J., … Lebedev, M. A. (2017). A novel paraplegia model in awake behaving macaques. J Neurophysiol, 118(3), 1800–1808. https://doi.org/10.1152/jn.00327.2017
Krucoff, Max O., Katie Zhuang, David MacLeod, Allen Yin, Yoon Woo Byun, Roberto Jose Manson, Dennis A. Turner, Laura Oliveira, and Mikhail A. Lebedev. “A novel paraplegia model in awake behaving macaques.J Neurophysiol 118, no. 3 (September 1, 2017): 1800–1808. https://doi.org/10.1152/jn.00327.2017.
Krucoff MO, Zhuang K, MacLeod D, Yin A, Byun YW, Manson RJ, et al. A novel paraplegia model in awake behaving macaques. J Neurophysiol. 2017 Sep 1;118(3):1800–8.
Krucoff, Max O., et al. “A novel paraplegia model in awake behaving macaques.J Neurophysiol, vol. 118, no. 3, Sept. 2017, pp. 1800–08. Pubmed, doi:10.1152/jn.00327.2017.
Krucoff MO, Zhuang K, MacLeod D, Yin A, Byun YW, Manson RJ, Turner DA, Oliveira L, Lebedev MA. A novel paraplegia model in awake behaving macaques. J Neurophysiol. 2017 Sep 1;118(3):1800–1808.

Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

September 1, 2017

Volume

118

Issue

3

Start / End Page

1800 / 1808

Location

United States

Related Subject Headings

  • Walking
  • Wakefulness
  • Spinal Cord Injuries
  • Paraplegia
  • Neurology & Neurosurgery
  • Neurological Rehabilitation
  • Muscle, Skeletal
  • Muscle Contraction
  • Male
  • Macaca mulatta