Neuronal Regulation and Locomotion in Rats Following Spinal Cord Injury: Reconciling Behavioral Scales With Neuroelectrophysiology
TL;DR
It is argued that relying solely on locomotor scales overestimates functional tract integrity, and it is advocated for a paradigm shift toward integrating synchronized behavioral and electrophysiological profiling to improve the predictive validity of preclinical SCI trials.
Abstract
Progress in translating spinal cord injury (SCI) therapies from bench to bedside remains bottlenecked by a critical paradox in preclinical phenotyping: the frequent divergence between behavioral recovery metrics and objective neurophysiological outcomes. For decades, the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale has served as the standard subjective metric for assessing hindlimb function in rodent models. However, while behavioral scales often capture substantial endogenous recovery and central pattern generator (CPG) autonomy, they frequently fail to correlate with objective neuro-electrophysiological metrics, such as motor and somatosensory evoked potentials (MEPs/SSEPs), particularly during the acute and sub-acute phases of injury. This perspective evaluates the neuroanatomical and pathophysiological mechanisms underlying this discrepancy. We dissect how the spatial distribution of contusive forces, the demyelination of anatomically spared fibers, and transient spinal shock alter early electrophysiological signaling without permanently arresting long-term behavioral plasticity. Furthermore, we highlight key neuroanatomical differences—specifically the dorsal preservation of the corticospinal tract in rodents versus the lateral architecture in humans—that complicate cross-species translation. Ultimately, we argue that relying solely on locomotor scales overestimates functional tract integrity, and we advocate for a paradigm shift toward integrating synchronized behavioral and electrophysiological profiling to improve the predictive validity of preclinical SCI trials.