Background/Objectives: Prior studies have noted varied, spontaneous motor recovery in rat strains after spinal cord injury (SCI), but systematic comparisons of different locomotor measurements across different severity and sexes are lacking. Hence, we quantified hindlimb utilization in male and female Sprague-Dawley (SD) and Wistar rats following moderate and severe SCI. Methods: Compression SCI was induced using a 15-g clip for 180 s for moderate SCI or a 50-g aneurysm clip for 60 s for severe SCI in male and female SD and Wistar rats. Measures of locomotor performance using the Basso–Beattie–Bresnahan (BBB), CatWalk gait analysis, and horizontal ladder tests were taken postoperatively and weekly for seven weeks. Results: BBB scores indicated greater spontaneous recovery in SD rats, with females showing higher scores than males following moderate and severe SCI. No sex or strain differences were observed in the horizontal ladder test. The CatWalk results indicated greater average hindlimb swing speed in SD rats following moderate SCI, but greater print area was observed in Wistar rats after severe SCI, although female SD rats had greater print area than either male SD or female Wistar rats following moderate SCI. Conclusions: The findings that SD rats, especially females, exhibited greater spontaneous motor recovery following moderate SCI indicate the need to consider the sex and strain of rats when conducting therapeutic testing following moderate SCI. The significance of these findings is that they should facilitate the use of appropriate rat models for translational research in SCI that can be applied to future clinical trials.

Spinal cord injury (SCI) is a neurological condition that leads to motor and sensory dysfunction. Emerging data indicate that combination therapies are promising, as they target multiple mechanisms. Photobiomodulation therapy (PBMT) has demonstrated the capacity to reduce inflammation, promote axonal regeneration, and improve motor function recovery. Polyethylene glycol (PEG) has shown neuroprotective effects and supports motor recovery following SCI. Here, we evaluated the effects of 660 nm PBMT and PEG-600, as monotherapies and in combination, on motor function recovery, axonal integrity, apoptosis, and inflammation in male and female rats following SCI. Male and female rats were randomized and assigned to PBMT, PEG-600, combination treatment, or vehicle groups. PBMT was initiated 30 min following injury and continued daily, while PEG-600 (10 µL) was injected locally at the injury site immediately after injury. Motor function was evaluated using BBB scores, and histological analyses were used to assess axonal integrity and neuronal survival, synaptic density, inflammation, and apoptosis. In male rats, PBMT and PEG monotherapies resulted in greater motor function recovery compared to the combined treatment. PBMT also enhanced markers of synaptic density and axonal integrity in male rats. In female rats, PBMT reduced apoptosis, while both PBMT and PEG monotherapies reduced microglial activation. Astrocyte activation was lower in PBMT-treated male rats compared to the vehicle group. PBMT as a monotherapy was more efficacious as a monotherapy than when combined with PEG-600. These data indicate that treatment response patterns may differ between male and female rats and suggest that combination of 660 nm PBMT and PEG-600 was less efficacious than each monotherapy.