High Thoracic Contusion Model for the Investigation of Cardiovascular Function after Spinal Cord Injury

Cardiovascular disease is the leading cause of death for individuals with spinal cord injury (SCI). Because of a lack of a standardized and accessible animal model for cardiovascular disease after SCI, few laboratories have conducted preclinical trials aimed at reinstating descending cardiovascular control. Here, we utilized common contusion methodology applied to the midline of the upper-thoracic cord of adult Wistar rats accompanied with telemetric blood pressure monitoring and FluoroGold retrograde neuronal tracing, as well as lesion site and lumbrosacral afferent immunohistochemistry. We demonstrate widespread cardiovascular (i.e., impaired resting hemodynamics, autonomic dysreflexia) and hindlimb dysfunction at 1 month post-injury. Further, we provide a description of the neuroanatomical changes that accompany cardiovascular abnormalities. Specifically, we describe 1) the injury site including white matter sparing as well as lesion volume, and their correlations to cardiovascular as well as motor outcomes; 2) the severity of injury-dependent changes in sympathoexcitatory medullary neuron spinal connectivity, as measured using FluoroGold tracing; and 3) the extent of aberrant afferent plasticity within the lumbosacral region of the spinal cord, which has been linked to the development of autonomic dysreflexia. We believe that this model, which utilizes equipment common to numerous SCI laboratories, can serve as a research standard for studies specifically aimed at investigating autonomic neuroprotective and regenerative strategies following SCI.