Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity

Abstract

As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that seek to strengthen the remaining spinal pathways with a view to improve motor function. To date, few, if any, of these interventions have been tested for their effectiveness to improve autonomic and cardiovascular (CV) function. As a first step to testing such therapies, we aimed to develop a model that has sufficient sparing of descending sympathetic pathways for these interventions to target yet induces robust CV impairment. Twenty-six Wistar rats were assigned to SCI (n = 13) or naïve (n = 13) groups. Animals were injured at the T3 spinal segment with 300 kdyn of force. Fourteen days post-SCI, left ventricular (LV) and arterial catheterization was performed to assess in vivo cardiac and hemodynamic function. Spinal cord lesion characteristics along with sparing in catecholaminergic and serotonergic projections were determined via immunohistochemistry. SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001). Our novel SCI model produced significant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.

A cross‐species validation of single‐beat metrics of cardiac contractility

“…up to 4 h post‐injury), and level of injury (i.e. T2−3) are sufficient to cause a marked decrement in cardiac contractile function, evidenced by a significant reduction in E es in both rodent and porcine models (Fossey et al., 2022; Poormasjedi‐Meibod et al., 2019; Squair et al., 2018; Wainman et al., 2021; Williams et al., 2020). Moreover, in a recent manuscript, describing a series of experiments in both rodents and individuals with SCI, we reported that SCI induces considerable contractile dysfunction post‐injury that occurs due to the loss of bulbospinal sympathetic control over the heart (Fossey et al., 2022).…”

“…Animals were randomly assigned to either naïve or with injury to the spinal cord (severe contusion injury at the T3 spinal level). All procedures associated with inducing injury and pre‐ and post‐operative care have been described in detail previously (Wainman et al., 2021). Briefly, rats were initially anaesthetized using an inhalant anaesthetic (5% isoflurane chamber induction, and maintenance on 1.5−2% isoflurane, Piramal Critical Care, Bethlehem, PA, USA) and received enrofloxacin (10 mg/kg; Bayer Animal Health, Shawnee, KS, USA), buprenorphine (0.5 mg/kg; Ceva Animal Health, Cambridge, ON, Canada) and warmed lactated Ringer solution (5 ml subcutaneously; Baxter Corporation, Portland, OR, USA).…”