Targeting diabetes-induced brain damage by photobiomodulation: evidence of multiorgan protection.

Diabetes-associated neuropathy and cognitive impairment result from sustained hyperglycemia, oxidative stress, mitochondrial dysfunction, and inflammation. Photobiomodulation (PBM) counteracts these by improving mitochondrial function and reducing oxidative and inflammatory stress. This study investigated the comparative therapeutic potential of PBM alone and in combination with Metformin and Insulin, in Streptozotocin-induced diabetic mice models. Pre- and post-treatment behavioral tests assessed nociception, sensorimotor performance, and memory. Histopathological analysis of the brain, sciatic nerve, and major organs, including heart, liver, kidney, and lungs, along with real-time polymerase chain reaction of neuroinflammatory markers (MPZ & BDNF), provided structural and molecular insights. All treatment groups showed marked improvement compared with diabetes controls, with combination therapy groups (PBM, Metformin, and PBM with Insulin) producing the most pronounced recovery in the majority of behavioral tests, histopathological analysis, and gene expression analysis. Monotherapies provided moderate yet meaningful protection. These results highlight the synergistic neuroprotective potential of PBM when combined with Metformin or Insulin and support these combination therapies as promising strategies for mitigating diabetes associated neuropathy and cognitive impairment.