Autonomic Dysreflexia Persists Following Acute Rehabilitation in Rats with Incomplete Contusive Spinal Cord Injury
Authors: Harman Kathryn A. , DeVeau Kathryn M. , Squair Jordan W. , West Christopher R. , Magnuson David SK. , Krassioukov Andrei V. 
Published: November 2023

Introduction

Disruption of autonomic pathways following spinal cord injury (SCI) leads to altered cardiovascular (CV) function and homeostasis. The level and completeness of injury have great ramifications on the clinical presentation of CV pathology. Severe cervical and high thoracic lesions disrupt supraspinal control of sympathetic preganglionic neurons of the heart and upper body vasculature, leading to a state in which episodic hypertensive crises known as autonomic dysreflexia (AD) can develop. Rodent studies utilizing complete transection of the upper thoracic cord have shown that appropriately‐timed rehabilitation has the ability to reduce the severity of AD and normalize cardiac function. To date, no study has examined the impact of acute rehabilitation on CV function in a more clinically relevant contusive SCI model. Our objective was to evaluate the effects of either passive hind limb cycling (PHLC) or active swimming therapy on the development and severity of AD following severe T2 contusion.

Methods

Male Wistar rats with severe T2 contusions (400 kDyn, 5 second dwell, Infinite Horizons Impactor), were randomly divided into three groups: Control (T2‐CON, n=7), PHLC (T2‐ PHLC, n=5), or Swim rehabilitation (T2‐SWIM, n=6). A fourth group received T10 severe contusions and served as injured controls with intact cardiac sympathetic preganglionic pathways (T10‐CON, n=6). Rehabilitation therapy began 7 days post injury, and lasted for three weeks (30 minutes per day, 5 days per week). Five weeks post injury, rats were implanted with telemetric blood pressure devices (Millar, TRM54P) and pressor responses (i.e. AD) induced by colorectal distension (CRD) were evaluated.

Results

Resting hemodynamics did not differ between T2‐ PHLC, T2‐SWIM, and T2‐CON groups. Animals that received T10 injuries developed resting tachycardia (all groups p < .05). Pressor responses to CRD varied considerably across animals, but were significantly greater in T2 contused animals than in T10‐CON (all groups p < .05), and neither rehabilitation approach was able to attenuate the hypertensive crisis in response to CRD. However, if each group was subdivided based on BBB score, animals with low BBB scores (≤ 6) in the PHLC group were not statistically different from T10‐CON (p = .055). Conversely, both T2‐CON and T2‐SWIM animals with low BBB scores exhibited greater pressor responses during CRD (both groups p < .05).

Conclusions

Using a clinically relevant contusive model of SCI, we show that neither PHLC nor active swimming rehabilitation has the ability to favorably impact CV responses to CRD in incompletely injured T2 rats. However, if the most severely injured animals are assessed separately (BBB scores ≤ 6), PHLC appears to improve CV homeostasis and reduce the severity of pressor responses during CRD. This data suggests a relationship between locomotor recovery and CV function independent of applied PHLC or swim exercise that may depend more on improvements in hind limb activity and/or tissue sparing at the injury epicenter.

Support or Funding Information

iCORD VISIT Scholarship, CIHR, CNF, Kentucky Spinal Cord and Head Injury Trust (P30 RR031159), NIH (R56 NS052292), and Friends for Micheal