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

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.