Multi-limb acquisition of motor evoked potentials and its application in spinal cord injury

The motor evoked potential (MEP) is an electrical response of peripheral neuro-muscular pathways to stimulation of the motor cortex. MEPs provide objective assessment of electrical conduction through the associated neural pathways, and therefore detect disruption due to a nervous system injury such as spinal cord injury (SCI). In our studies of SCI, we developed a novel, multi-channel set-up for MEP acquisition in rat models. Unlike existing electrophysiological systems for SCI assessment, the set-up allows for multi-channel MEP acquisition from all limbs of rats and enables longitudinal monitoring of injury and treatment for in vivo models of experimental SCI. The article describes the development of the set-up and discusses its capabilities to acquire MEPs in rat models of SCI. We demonstrate its use for MEP acquisition under two types of anesthesia as well as a range of cortical stimulation parameters, identifying parameters yielding consistent and reliable MEPs. To validate our set-up, MEPs were recorded from a group of 10 rats before and after contusive SCI. Upon contusion with moderate severity (12.5mm impact height), MEP amplitude decreased by 91.36±6.03%. A corresponding decline of 93.8±11.4% was seen in the motor behavioral score (BBB), a gold standard in rodent models of SCI.

[1]  Hasan Al-Nashash,et al.  Spinal Cord Injury Detection and Monitoring Using Spectral Coherence , 2009, IEEE Transactions on Biomedical Engineering.

[2]  B. Kakulas,et al.  A review of the neuropathology of human spinal cord injury with emphasis on special features. , 1999, The journal of spinal cord medicine.

[3]  Alexander Sasha Rabchevsky,et al.  Rat models of traumatic spinal cord injury to assess motor recovery. , 2007, ILAR journal.

[4]  M. Fehlings,et al.  Autonomic dysreflexia and primary afferent sprouting after clip-compression injury of the rat spinal cord. , 2001, Journal of neurotrauma.

[5]  C. Kalkman,et al.  Influence of isoflurane on myogenic motor evoked potentials to single and multiple transcranial stimuli during nitrous oxide/opioid anesthesia. , 1998, Neurosurgery.

[6]  M. Fehlings,et al.  The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. , 1989, Electroencephalography and clinical neurophysiology.

[7]  Nitish V Thakor,et al.  Characterization of Graded Multicenter Animal Spinal Cord Injury Study Contusion Spinal Cord Injury Using Somatosensory-Evoked Potentials , 2010, Spine.

[8]  J. Graybeal,et al.  Preservation of Neurogenic Motor‐Evoked Potentials During Isoflurane Electroencephalographic Burst Suppression in Rats , 1994, Spine.

[9]  K. Sugahara,et al.  Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord-evoked potentials monitoring during aortic occlusion in rats , 2007, European Spine Journal.

[10]  R. Hicks,et al.  Some effects of isoflurane on I waves of the motor evoked potential. , 1992, British journal of anaesthesia.

[11]  R. Hopf,et al.  Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials in the rat. , 2001, Somatosensory & motor research.

[12]  C. B. Shields,et al.  Small-Molecule Protein Tyrosine Phosphatase Inhibition as a Neuroprotective Treatment after Spinal Cord Injury in Adult Rats , 2008, The Journal of Neuroscience.

[13]  R. Hopf,et al.  The effect of ketamine/xylazine anesthesia on sensory and motor evoked potentials in the rat , 2002, Spinal Cord.

[14]  Ching Zhu,et al.  Comparison of Isoflurane Effects on Motor Evoked Potential and F Wave , 2000, Anesthesiology.

[15]  S. Whittemore,et al.  Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat , 2005, Experimental Neurology.

[16]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[17]  Nitish V. Thakor,et al.  Evoked potential versus behavior to detect minor insult to the spinal cord in a rat model , 2009, Journal of Clinical Neuroscience.

[18]  A. Patil,et al.  Cortically evoked motor action potential in spinal cord injury research. , 1985, Neurosurgery.

[19]  B. Kakulas,et al.  Neuropathology: the foundation for new treatments in spinal cord injury , 2004, Spinal Cord.

[20]  V. Dietz,et al.  Impaired facilitation of motor evoked potentials in incomplete spinal cord injury , 2005, Journal of Neurology.

[21]  D. Yoon,et al.  Human mesenchymal stem cell transplantation promotes functional recovery following acute spinal cord injury in rats. , 2007, Acta neurobiologiae experimentalis.

[22]  D. Burke,et al.  Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury , 2007, Experimental Neurology.

[23]  C. Kalkman,et al.  Spinal cord monitoring: somatosensory- and motor-evoked potentials. , 2001, Anesthesiology clinics of North America.

[24]  K. Klose,et al.  Isoflurane-induced attenuation of motor evoked potentials caused by electrical motor cortex stimulation during surgery. , 1991, Journal of neurosurgery.

[25]  D. Burke,et al.  Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury , 2009, Neuroscience.

[26]  A. Grippo,et al.  Motor evoked potentials in multiple sclerosis patients without walking limitation: amplitude vs. conduction time abnormalities , 2007, Journal of Neurology.

[27]  M. Papadopoulos,et al.  Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. , 2008, Brain : a journal of neurology.

[28]  M. Beattie,et al.  Degeneration and Sprouting of Identified Descending Supraspinal Axons after Contusive Spinal Cord Injury in the Rat , 2001, Experimental Neurology.

[29]  C. Brösamle,et al.  Cracking the black box – and putting it back together again: Animal models of spinal cord injury , 2006 .

[30]  N. Thakor,et al.  Slope analysis of somatosensory evoked potentials in spinal cord injury for detecting contusion injury and focal demyelination , 2010, Journal of Clinical Neuroscience.

[31]  J. A. Gruner,et al.  4-Aminopyridine enhances motor evoked potentials following graded spinal cord compression injury in rats , 1999, Brain Research.

[32]  Michael S. Beattie,et al.  Graded Histological and Locomotor Outcomes after Spinal Cord Contusion Using the NYU Weight-Drop Device versus Transection , 1996, Experimental Neurology.

[33]  R. Quencer,et al.  Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. , 1993, Advances in neurology.

[34]  X. Navarro,et al.  Differential motor and electrophysiological outcome in rats with mid-thoracic or high lumbar incomplete spinal cord injuries , 2006, Brain Research.

[35]  J. Fawcett,et al.  Repair of spinal cord injuries: where are we, where are we going? , 2002, Spinal Cord.

[36]  R. Nashmi,et al.  Serial recording of somatosensory and myoelectric motor evoked potentials: role in assessing functional recovery after graded spinal cord injury in the rat. , 1997, Journal of neurotrauma.

[37]  Gracee Agrawal,et al.  A comparative study of recording procedures for motor evoked potential signals , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[38]  Nitish V. Thakor,et al.  Effect of MOG sensitization on somatosensory evoked potential in Lewis rats , 2009, Journal of Neurological Sciences.

[39]  J. Knight,et al.  Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience , 1981, Laboratory animals.