title: Electrophysiological biomarkers of neuromodulatory strategies to recover motor function after spinal cord injury.
abstract: The spinal cord contains the circuitry to control posture and locomotion after complete paralysis, and this circuitry can be enabled with epidural stimulation [electrical enabling motor control (eEmc)] and/or administration of pharmacological agents [pharmacological enabling motor control (fEmc)] when combined with motor training. We hypothesized that the characteristics of the spinally evoked potentials after chronic administration of both strychnine and quipazine under the influence of eEmc during standing and stepping can be used as biomarkers to predict successful motor performance. To test this hypothesis we trained rats to step bipedally for 7 wk after paralysis and characterized the motor potentials evoked in the soleus and tibialis anterior (TA) muscles with the rats in a non-weight-bearing position, standing and stepping. The middle responses (MRs) to spinally evoked stimuli were suppressed with either or both drugs when the rat was suspended, whereas the addition of either or both drugs resulted in an overall activation of the extensor muscles during stepping and/or standing and reduced the drag duration and cocontraction between the TA and soleus muscles during stepping. The administration of quipazine and strychnine in concert with eEmc and step training after injury resulted in larger-amplitude evoked potentials [MRs and late responses (LRs)] in flexors and extensors, with the LRs consisting of a more normal bursting pattern, i.e., randomly generated action potentials within the bursts. This pattern was linked to more successful standing and stepping. Thus it appears that selected features of the patterns of potentials evoked in specific muscles with stimulation can serve as effective biomarkers and predictors of motor performance.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California;
authors.forename: Parag
authors.initials: P
authors.lastname: Gad
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California; Brain Research Institute, University of California, Los Angeles, California;
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California;
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Choe
authors.affiliation: Department of Neuroscience, University of California, Los Angeles, California;
authors.forename: Jack
authors.initials: J
authors.lastname: Creagmile
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California;
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California; Pavlov Institute of Physiology, St. Petersburg, Russia; and Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
authors.forename: Yury
authors.initials: Y
authors.lastname: Gerasimenko
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, California; Department of Neurobiology, University of California, Los Angeles, California; Department of Neurosurgery, University of California, Los Angeles, California; Brain Research Institute, University of California, Los Angeles, California; vre@ucla.edu.
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018684:Glycine Agents / Q000494:pharmacology; D006614:Hindlimb / Q000294:innervation; D018482:Muscle, Skeletal / Q000502:physiology*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy*; D013331:Strychnine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018684:Glycine Agents; D017366:Serotonin Receptor Agonists; D011814:Quipazine; D013331:Strychnine
keywords: epidural stimulation; evoked potentials; quipazine; spinal cord injury; strychnine