Jerry Silver, PhD
Professor, Department of Neurosciences, Case Western Reserve University School of Medicine

Abstract
Recovery of Forearm and Fine Digit Function after Chronic Spinal Cord Injury
Spinal cord injuries, for which there are limited effective clinical treatments, result in enduring paralysis and hypoesthesia due, in part, to the inhibitory microenvironment that develops and limits regeneration/sprouting, especially during chronic stages. Recently, we discovered that targeted enzymatic modulation of the potently inhibitory chondroitin sulfate proteoglycan (CSPG) component of the extracellular and perineuronal net (PNN) matrix via Chondroitinase ABC (ChABC) can rapidly restore robust respiratory function to the previously paralyzed hemi-diaphragm after remarkably long times post-injury (up to 1.5 years) following a cervical level 2 lateral hemi-transection. Importantly, ChABC treatment at cervical level 4 in this chronic model also elicited rapid, albeit modest, improvements in upper arm function. In my talk I will also present new work where we sought to further optimize and elucidate the capacity for nerve sprouting and/or regeneration to restore gross as well as fine motor control of the forearm and digits at lengthy chronic stages post injury. However, instead of using ChABC, we utilized a novel and more clinically relevant systemic, non-invasive combinatorial treatment strategy designed to both reduce and overcome inhibitory CSPGs simultaneously and spatially extensively. Following a three-month upper cervical spinal hemi-lesion, we show that the combined treatment has a profound effect on functional recovery of the chronically paralyzed forelimb and paw, specifically during walking as well as precision movements of the digits. Our exciting pre-clinical findings will begin to dramatically enhance our understanding of the basic mechanisms underlying functionally beneficial regenerative events occurring at chronic injury stages for clinically relevant translational benefits.

Bio
Dr. Silver earned his PhD from Case Western Reserve in 1974 and received the Steuer Memorial Award for Meritorious Original Research. He did post-doctoral work at Harvard University. Dr. Silver is currently Professor in the Neurosciences Department at Case Western Reserve University. He is a recipient of several prestigious awards. In 2003, he was awarded the Ameritec Prize for significant accomplishments toward a cure for paralysis and the Christopher Reeve-Joan Irvine Research Medal for critical contributions that may lead to the promotion of repair of the damaged spinal cord. Dr. Silver received the 2008 Erica Nader Award, given through the American Spinal Injury Association. In 2011, he became a fellow of the American Association for the Advancement of Science. Dr. Silver has served on many editorial boards including Experimental Neurology where he was Section Editor and is currently associate editor of the Journal of Neurotrauma. He has produced more than 190 publications.