title: Repeated transcranial low-level laser therapy for traumatic brain injury in mice: biphasic dose response and long-term treatment outcome.
abstract: We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/cm2, 25 mW/cm2) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6-weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis.
authors.affiliation: Dept of Otorhinolaryngology, Head and Neck Surgery, Ruikang Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, China.|Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Weijun
authors.initials: W
authors.lastname: Xuan
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Liyi
authors.initials: L
authors.lastname: Huang
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D000818:Animals; D001921:Brain / Q000528:radiation effects*; D000070642:Brain Injuries, Traumatic / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D028022:Low-Level Light Therapy; D051379:Mice; D016896:Treatment Outcome
chemical_list: D005904:Glial Fibrillary Acidic Protein; C528900:glial fibrillary astrocytic protein, mouse
keywords: LLLT; Morris water maze; Traumatic brain injury; biphasic dose response; controlled cortical impact mouse model; glial fibrillary acidic protein; photobiomodulation; reactive gliosis