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 Service
National 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)