Transcranial low-level light therapy produces neuroprotection, neurogenesis and BDNF after TBI in mice

We have previously shown that transcranial low level light therapy (LLLT) can ameliorate brain damage in mice subjected to traumatic brain injury and improve neurological function. We used 810-nm laser and delivered 18 J/cm2 at an irradiance 25 mW/cm2. LLLT was either delivered once at 4 hours after controlled cortical impact TBI, once a day for 3 days, or once a day for 14 days. One and 3 applications of LLLT had beneficial effects on the mice, with 3 being better than 1, but 14 applications had no beneficial effect. We now report immunofluorescence studies in mouse brain sections that offer some explanation for this intriguing finding. Mice were injected for a week before sacrifice with a marker for proliferating cells (BrdU), and the neutrotrophin BDNF (brain derived neurotrophic factor) was stained for. We found increased BrdU incorporation indicating proliferating cells in the dentate gyrus of the hippocampus, the subventricular layer of the lateral ventricle, as well as the brain tissue surrounding the cortical lesion. Interestingly these cells were more abundant at 7 days than at 28 days post TBI. Co-labeling of BrdU with Neu-N was performed indicating that the proliferating cells were in fact neuronal in nature. Caspase-3 was used to study the neuronal death pathways activated after TBI and laser treatments. Mice with 3 laser treatments had much more BrdU incorporation than mice with 14. Upregulation of BDNF was seen at 7 days, a possible indication that neuroprogenitor cells may have migrated there from sites of neurogenesis. Taken together these data suggest that transcranial LLLT may have applications beyond TBI in areas such as neurodegenerative disease and psychiatric disorders.