*P. D. GANZER1, E. C. MEYERS1, B. R. SOLORZANO2, K. S. ADCOCK2, N. M. ROBERTSON2, J. T. JAMES2, A. RUIZ2, A. M. BECKER3, M. P. GOLDBERG3, D. T. PRUITT1, J. K. MOY2, S. N. HASSLER2, T. J. PRICE2, M. A. LANE4, W. M. GLUF5, M. P. KILGARD2, R. L. RENNAKER1;
1Bioengineering, Univ. of Texas At Dallas, Richardson, TX; 2Sch. of Behavioral Brain Sci., Univ. of Texas at Dallas, Richardson, TX; 3Neurol. and Neurotherapeutics, UT Southwestern Med. Ctr., Dallas, TX; 4Drexel Univ. Col. of Med., Philadelphia, PA; 5Dept. of Neurology. Surgery, Univ. of Texas Southwestern Med. Ctr., Dallas, TX
Abstract: Cervical spinal cord injury (cSCI) leads to long-lasting impairments in forelimb function. The location and extent of cSCI determine the subsequent impairment. It has long been assumed that the degree of functional recovery is similarly determined by the lesion. There is growing evidence that this assumption is incorrect. We tested the hypothesis that functional recovery following chronic cSCI is primarily limited by ineffective neural plasticity. Rats were first trained to proficiency on the isometric pull task to assess volitional forelimb strength and given a C5/C6 hemicontusion. Repeatedly pairing vagus nerve stimulation (VNS) with forelimb movement beginning six weeks after cSCI promoted 75% more recovery of forelimb function compared to intense rehabilitation alone. In spite of significant forelimb strength enhancement, we observed no differences in awake behaving forelimb muscular dynamics or forelimb pain between groups. We next used intracortical mappings of motor cortex and retrograde transsynaptic tracing from the forelimb musculature to examine neural plasticity. The addition of VNS as an adjuvant to rehabilitation substantially improved the anatomical and physiological connectivity of forelimb grasping musculature with motor cortex, without altering the extent of spinal damage. These findings suggest that neural plasticity, and not lesion extent, primarily limits recovery from cSCI. However, enhanced recovery from hemicontusion does not suggest that VNS paired with rehabilitation will improve recovery from cSCI in humans because most patients have bilateral cervical spinal damage. To address this limitation, we repeated the behavioral assessments above in rats with midline cervical spinal contusions. Repeatedly pairing VNS with forelimb movement beginning eight weeks after bilateral cSCI again enhanced recovery of forelimb function compared to intense rehabilitation alone. These findings provide new hope for patients and suggest that plasticity-based therapies may prove to be clinically useful.
P.D. Ganzer: None. E.C. Meyers: None. B.R. Solorzano: None. K.S. Adcock: None. N.M. Robertson: None. J.T. James: None. A. Ruiz: None. A.M. Becker: None. M.P. Goldberg: None. D.T. Pruitt: None. J.K. Moy: None. S.N. Hassler: None. T.J. Price: None. M.A. Lane: None. W.M. Gluf: None. M.P. Kilgard: None. R.L. Rennaker: None.