Cardiovascular and Locomotor Recovery Following Hindlimb Muscle Stretching of Rodents with a Clinically Relevant Model of Spinal Cord Injury

Physical therapy stretching remains one of the most prevalent therapies for patients with spinal cord injury (SCI); however, we have previously shown that daily hindlimb muscle stretching of rats following a T10 SCI significantly disrupts their hindlimb locomotor function, likely through maladaptive sprouting of nociceptive afferents and modulation of lumbar spinal circuitry. Despite these clinically significant findings, mid-thoracic contusion models do not represent a majority of clinical injuries and are not effective for modeling the loss of cardiovascular control and autonomic complications that patients with higher level SCI experience. Therefore, the objective of the current study was to examine the effects of hindlimb stretching on the locomotor and cardiovascular function of rats with a T2 SCI. Twenty-six female Sprague-Dawley rats received a moderate T2 contusion (25 g/cm) and were divided into SCI Control (n = 14) and Stretched (n = 12) groups. Our daily hindlimb stretching protocol was initiated at week 5 post-SCI and administered 5 days/week for 4 weeks before a portion of the animals from each group were euthanized. The remaining animals (Control: n = 8, Stretched: n = 6) recovered for 3 weeks before euthanasia. Locomotor function was assessed using the Basso, Beattie and Bresnahan Open Field Locomotor Scale and kinematic gait analysis. Additionally, cardiovascular indices were collected using echocardiography at baseline, pre-stretching, post-stretching, and post-recovery timepoints. Four weeks of daily stretching led to transient disruption of locomotor function as well as reduced overnight activity followed by robust improvements in locomotion once stretching was no longer administered. Although stretching did not appear to have a dramatic effect on cardiovascular indices, both groups displayed significant changes over time in cardiac output and stroke volume. Furthermore, immunohistochemistry staining revealed that stretching did not exacerbate Calcitonin Gene-Related Protein (CGRP+) nociceptor sprouting in the lumbar dorsal horn, contrary to the effects we have shown in T10 stretched animals. Overall, these results indicate that hindlimb stretching following a high-thoracic SCI does not appear to aberrantly modulate lumbar spinal circuitry as has been shown in low thoracic injuries. Additionally, stretching combined with a T2 SCI does not result in cardiovascular dysfunction, although future work must be conducted to determine whether stretching triggers autonomic events and maladaptive plasticity near the spinal lesion.