Potential for Transcranial Laser or LED Therapy to Treat Stroke, Traumatic Brain Injury, and Neurodegenerative Disease

Abstract

Near-infrared (NIR) light passes readily through the scalp and skull and a small percentage of incident power density can arrive at the cortical surface in humans.1 The primary photoreceptors for red and NIR light are mitochondria, and cortical neurons are exceptionally rich in mitochondria. It is likely that brain cells are ideally set up to respond to light therapy. The basic biochemical pathways activated by NIR light, e.g., increased adenosine-5’-triphosphate (ATP) production, and signaling pathways activated by reactive oxygen species, nitric oxide release, and increased cyclic adenosine monophosphate (AMP) all work together to produce beneficial effects in brains whose function has been compromised by ischemia, traumatic injury, or neurodegeneration. One of the main mechanisms of action of transcranial light therapy (TLT) is to prevent neurons from dying, when they have been subjected to some sort of hypoxic, traumatic, or toxic insult. This is probably because of light-mediated upregulation of cytoprotective gene products such as antioxidant enzymes, heat shock proteins, and anti-apoptotic proteins. Light therapy in vitro has been shown to protect neurons from death caused by methanol,2 cyanide or tetrodotoxin, 3 and amyloid beta peptide.4 There is also probably a second mechanism operating in TLT; increased neurogenesis. Neurogenesis is the generation of neuronal precursors and birth of new neural cells.5 Two key sites for adult neurogenesis include the subventricular zone (SVZ) of the lateral ventricles, and the subgranular layer (SGL) of the dentate gyrus in the hippocampus.6 Neurogenesis can be stimulated by physiological factors, such as growth factors and environmental enrichment, and by pathological processes, including ischemia and neurodegeneration.7 Adult neurogenesis (in the hippocampus particularly) is now recognized as a major determinant of brain function both in experimental animals and in humans. Neural progenitor cells in their niche in the SGL of the dentate gyrus give birth to newly formed neurons that are thought to play a role in brain function, particularly in olfaction and in hippocampal-dependent learning and memory. In small animal models neurogenesis can be readily detected by incorporation of bromodeoxyuridine (BrdU), injected before euthanasia, into proliferating brain cells. Increased neurogenesis after TLT, has been demonstrated in a rat model of stroke,9 and in the Hamblin laboratory after TLT for acute traumatic brain injury (TBI) in mice (W. Xuan, T. Ando, et al., unpublished data). These two mechanisms of action of TLT in ameliorating brain damage (prevention of neuronal death and increased neurogenesis) have motivated studies in both animals and humans for diverse brain disorders and diseases. TLT for acute stroke is the most developed,10 but acute TBI has also been shown to benefit from TLT.11 These areas are reviewed further.United States. Dept. of Veterans Affairs. Medical Research ServiceNational Institutes of Health (U.S.) (Grant R01AI50875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense. Congressionally Directed Medical Research Programs ( Program in TBI W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (F9950-04-1-0079