Low‐level laser therapy (810 nm) protects primary cortical neurons against excitotoxicity in vitro

Abstract

Excitotoxicity describes a pathogenic process whereby death of neurons releases large amounts of the excitatory neurotransmitter glutamate, which then proceeds to activate a set of glutamatergic receptors on neighboring neurons (glutamate, N-methyl-D-aspartate (NMDA), and kainate), opening ion channels leading to an influx of calcium ions producing mitochondrial dysfunction and cell death. Excitotoxicity contributes to brain damage after stroke, traumatic brain injury, and neurodegenerative diseases, and is also involved in spinal cord injury. We tested whether low level laser (light) therapy (LLLT) at 810-nm could protect primary murine cultured cortical neurons against excitotoxicity in vitro produced by addition of glutamate, NMDA or kainate. Although the prevention of cell death was modest but significant, LLLT (3 J/cm2 delivered at 25 mW/cm2 over 2 min) gave highly significant benefits in increasing ATP, raising mitochondrial membrane potential, reducing intracellular calcium concentrations, reducing oxidative stress and reducing nitric oxide. The action of LLLT in abrogating excitotoxicity may play a role in explaining its beneficial effects in diverse central nervous system pathologies. ((Figure: 5a)) Effect of 810-nm laser on intracellular reactive oxygen species (ROS) in cortical neurons with excitotoxicity

Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As) Augments Dermal Wound Healing in Immunosuppressed Rats

“…The earlier finding also corroborate our results and suggest that laser irradiation at 10 Hz mode was most effective for improving neurological outcome in traumatic brain injury and proposed the possible hypothesis that occurrence of positive resonance between the frequency of the pulsed (4–10 Hz) light and brain wave [25]. Increase production of ATP endorsed by in-vitro finding of Huang et al, who evaluated neurons protection ability of 810 nm laser against excitotoxicity in primary cortical neurons [45]. …”

Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice

“…First is the ability of tLLLT to protect tissue at risk of dying by upregulating cytoprotective pathways such as anti-apoptotic proteins. 38 The effect of tLLLT on increasing the mitochondrial membrane potential 39,40 may stabilize the mitochondria and/or prevent the opening of the mitochondrial permeability transition pore that is a well-known initiator of apoptosis. 41 Caspase-3 is known to be activated via both extrinsic (cell ligands) and intrinsic (mitochondrial assembly of pro-apoptotic factors) pathways in apoptotic cells.…”

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

“…In normal cells, absorption of light by Cox leads to an increase in mitochondrial membrane potential and a short burst of ROS is produced. However when the mitochondrial membrane potential is low because of pre-existing oxidative stress [63], excitotoxicity [64], or inhibition of electron transport [63], light absorption leads to an increase in mitochondrial membrane potential towards normal levels and the production of ROS is lowered.…”

“…It should be noted that PBM usually leads to an increase in intracellular Ca 2+ as shown by fluorescent probes [68]. However when intracellular Ca 2+ levels have been artificially raised (for instance by causing excitotoxicity with excess glutamate), then PBM can produce a drop in intracellular calcium and protect the neurons from dying [64]. The increase in calcium seen after PBM could also be a result of the release of Ca 2+ from intracellular stores [69].…”