Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury

Abstract

Recent preclinical advances highlight the therapeutic potential of treatments aimed at boosting regeneration and plasticity of spinal circuitry damaged by spinal cord injury (SCI). With several promising candidates being considered for translation into clinical trials, the SCI community has called for a non-human primate model as a crucial validation step to test efficacy and validity of these therapies prior to human testing. The present paper reviews the previous and ongoing efforts of the California Spinal Cord Consortium (CSCC), a multidisciplinary team of experts from 5 University of California medical and research centers, to develop this crucial translational SCI model. We focus on the growing volumes of high resolution data collected by the CSCC, and our efforts to develop a biomedical informatics framework aimed at leveraging multidimensional data to monitor plasticity and repair targeting recovery of hand and arm function. Although the main focus of many researchers is the restoration of voluntary motor control, we also describe our ongoing efforts to add assessments of sensory function, including pain, vital signs during surgery, and recovery of bladder and bowel function. By pooling our multidimensional data resources and building a unified database infrastructure for this clinically relevant translational model of SCI, we are now in a unique position to test promising therapeutic strategies’ efficacy on the entire syndrome of SCI. We review analyses highlighting the intersection between motor, sensory, autonomic and pathological contributions to the overall restoration of function.

Tracking trauma-induced structural and functional changes above the level of spinal cord injury

“…cyst formation) [56], cortical reorganization [31] and the inherent low capacity of repair [57]. In particular, rodent and primate models of SCI have demonstrated progressive axonal anterograde and retrograde degeneration of spinal pathways with subsequent neuronal changes at multiple levels [58][59][60].…”

Radiographic and Magnetic Resonance Imaging Identification of Thoracolumbar Spine Variants with Implications for the Positioning of the Conus Medullaris in Rhesus Macaques

“…These models represent important tools for continued progress in translational research and include injuries to the spinal cord in rhesus macaques at the cervical (Rosenzweig et al, ; Nout et al, 2012b), thoracic (Courtine et al, ) and lumbosacral levels (Ohlsson et al, ). Comprehensive and clinically relevant outcome measures allow for the evaluation of spontaneous plasticity of spinal cord circuitries and for preclinical testing of new treatment strategies in these nonhuman primate models (Nout et al, 2012a; Nielson et al, ).…”

The importance of the quadruped animal model in functional neurorehabilitation in the human biped

“…Regardless of the line of thought, there must be coordination between the forelimbs and hind limbs (Cazalets & Butrand, 2000;Nathan, Smith & Deacor, 1996), as well as memorization of this coordination (Nielsen, et al, 2015;Zhong et al, 2012).…”

“…Several studies have demonstrated how repeated rehabilitation exercises that stimulate the afferent and efferent sensory-motor pathways allow the spinal neural circuits to memorize the rehabilitation exercises which were practiced, and thus the neurorehabilitation will depend on repetition and qua-lity of the locomotor training (Nielsen et al, 2015;Zhong et al, 2012).…”