Photobiomodulation therapy and polyethylene glycol as monotherapy versus combination treatment in male and female rats following spinal cord injury

Abstract

Abstract Purpose Spinal cord injury (SCI) is a neurological disorder that causes motor and sensory dysfunction. Recent studies suggest that combination therapies are promising, as they target multiple mechanisms. Photobiomodulation therapy (PBMT) has been shown to reduce inflammation, promote axonal regeneration, and improve motor function recovery. Polyethylene glycol (PEG) has shown neuroprotective effects and supports motor recovery following SCI. The aim of this study was to evaluate 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. Methods Male and female rats were randomly assigned to PBMT, PEG-600, combination treatment, or vehicle groups. PBMT was initiated 30 minutes after 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 performed to assess axonal integrity and neuronal survival, synaptic density, inflammation, and apoptosis. Results 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 monotherapy groups showed reduced microglial activation. Astrocyte activation was lower in PBMT-treated male rats compared to the vehicle group. Conclusion PBMT as a monotherapy showed greater efficacy than combination treatment with PEG-600. Our findings highlight sex-dependent responses and suggest that combination treatments may, in some cases, reduce the efficacy of monotherapies.