Peripheral Nerve Grafts after Cervical Spinal Cord Injury in Adult Cats Marie-Pascale Côté, Ph.D. 1 , Amgad Hanna, M.D. 2 , Michel A. Lemay, Ph.D. 1 , Karen Ollivier- Lanvin, Ph.D. 1 , Lauren Santi, B.S. 1 , Kassi Miller, B.S. 1 , Rebecca Monaghan, B.S. 1 , and John D. Houlé, Ph.D. 1 1 Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129 2 Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, 19104 Abstract Peripheral nerve grafts (PNG) into the rat spinal cord support axon regeneration after acute or chronic injury, with synaptic reconnection across the lesion site and some level of behavioral recovery. Here, we grafted a peripheral nerve into the injured spinal cord of cats as a preclinical treatment approach to promote regeneration for eventual translational use. Adult female cats received a partial hemisection lesion at the cervical level (C7) and immediate apposition of an autologous tibial nerve segment to the lesion site. Five weeks later, a dorsal quadrant lesion was performed caudally (T1), the lesion site treated with Chondroitinase ABC two days later to digest growth inhibiting extracellular matrix molecules, and the distal end of the PNG apposed to the injury site. After 4–20 weeks, the grafts survived in 10/12 animals with several thousand myelinated axons present in each graft. The distal end of 9/10 grafts was well apposed to the spinal cord and numerous axons extended beyond the lesion site. Intraspinal stimulation evoked compound action potentials in the graft with an appropriate latency illustrating normal axonal conduction of the regenerated axons. Although stimulation of the PNG failed to elicit responses in the spinal cord distal to the lesion site, the presence of c-Fos immunoreactive neurons close to the distal apposition site indicates that regenerated axons formed functional synapses with host neurons. This study demonstrates the successful application of a nerve grafting approach to promote regeneration after spinal cord injury in a non-rodent, large animal model. Keywords spinal cord injury; regeneration; peripheral nerve graft; cat; c-Fos; chondroitinase INTRODUCTION Traumatic insult to the spinal cord induces both immediate mechanical damage and subsequent tissue degeneration leading to substantial physiological, biochemical and © 2010 Elsevier Inc. All rights reserved. Corresponding author: John D. Houlé, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, phone and fax: 215-991-8295; 215-843-9082, jhoule@drexelmed.edu. 2 Present address: Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI 53792 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Exp Neurol. Author manuscript; available in PMC 2011 September 1. Published in final edited form as: Exp Neurol. 2010 September ; 225(1): 173–182. doi:10.1016/j.expneurol.2010.06.011. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript