It has been known for many years that low levels of laser or non-coherent light in the red or near-infrared spectrum (LLLT) accelerate some phases of wound healing, but the benefits of LLLT in wound healing and medicine in general are still controversial. Partly this may be explained by the complicated dosimetry that pertains with regard to coherence, monochromaticity, wavelength, total fluence, pulse-structure, polarization state, power density and treatment repetition.  However, another major reason for the non-acceptance by the general medical community is the widespread uncertainty about the molecular, cellular and tissue mechanisms that transduce signals from the incident photons via chromophores and signaling pathways to the observed biological effects.  
We have been investigating these events and have discovered that a likely mechanism that applies in LLLT involves alteration of mitochondrial respiration that both increases cellular ATP levels and at the same time produces intracellular reactive oxygen species (ROS). We believe that these ROS activate cellular pathways designed to cope with low levels of oxidative stress. Redox-sensitive transcription factors such as NF-kB are activated, leading to expression of an array of gene products that prevent apoptosis and cell death, stimulate fibroblast proliferation, migration and collagen synthesis, modulate the inflammatory and anti-oxidant response, and stimulate angiogenesis and tissue repair.
Neuronal cells respond well to LLLT due to their high mitochondrial activity and we have shown that in vitro LLLT has a biphasic dose response, whereby a small amount of light is beneficial while a large amount of light loses the benefit and can be harmful. We have shown that LLLT can protect cultured cortical neurons from oxidative stress and from excitotoxicity.

 

Related Publications
Hamblin MR, Demidova TN. Mechanisms of Low Level Light Therapy – an Introduction. Proc SPIE; 2006; Vol 6140., art. no. 61001 1-12.

Demidova TN, Hamblin MR. Wound healing stimulation in mice by low-level light. Proc SPIE; 2006; Vol 6140. art. no.61400C 1-9

Hamblin MR, Demidova-Rice TN. Cellular chromophores and signaling in LLLT. Proc SPIE 6428. 2007; DOI: 10.1117/12.712885.

Hamblin MR. The role of nitric oxide in low level light therapy. Proc SPIE 6846, 2008; DOI: 10.1117/12.764918
Chen AC-H, Arany PR, Huang Y-Y, Tomkinson EM, Saleem T, Yull FE, Blackwell TS, Hamblin MR. Low level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. Proc SPIE Vol. 7165, 71650B. 2009. doi: 10.1117/12.809605

Chen AC-H, Huang Y-Y, Arany PR, Hamblin MR. Role of reactive oxygen species in low level light therapy. Proc SPIE Vol. 7165, 716502, 2009. doi: 10.1117/12.814890

Arany PR, Chen AC-H, Hunt T, Mooney D, Hamblin MR. Role of ROS-mediated TGF beta activation in laser photobiomodulation. Proc SPIE Vol. 7165, 71650C, 2009. doi: 10.1117/12.809839

Huang Y-Y, Chen A C-H, Carroll JD. Hamblin MR. Biphasic dose response in low-level light therapy. Dose Response Journal, 2009, 7, 358-383

Hashmi JT, Huang Y-Y, Sharma SK, Kurup DB, De Taboada L, Carroll JD, Hamblin MR. Effect of pulsing in low-level light therapy. Laser Surg Med, 2010, 42:450–466.

Hamblin, MR. Introduction to Experimental and Clinical Studies Using Low-Level Laser (Light) Therapy (LLLT). Lasers Surg Med, 2010; 42:447–449

Chen AC, Huang YY, Sharma SK, Hamblin MR. Effects of 810-nm Laser on Murine Bone-Marrow-Derived Dendritic Cells. Photomed Laser Surg. 2011, 29 (6), 383–389

Chen AC, Arany P, Huang YY, Tomkinson EM, Sharma SK Kharkwal GB, Saleem T, Mooney D, Yull FE, Blackwell TS, Hamblin MR. Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS ONE, 2011, 6 (7) e22453

Sharma SK, Kharkwal GB, Sajo M, Huang YY, De Taboada L, McCarthy T, Hamblin MR.   Dose response effects of 810-nm laser-light on mouse primary cortical neurons Lasers Surg Med, 2011, 43(8):851-9.

Huang YY Sharma SK, Carroll JD, Hamblin MR. Biphasic dose response in low-level light therapy – An update. Dose Response Journal, 2011, 9(4): 602-618.

Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy, Ann Biomed Eng, 2012, 40(2):516-33. DOI: 10.1007/s10439-011-0454-7.

Assis L, Moretti AI, Abrahão TB, de Souza HP, Hamblin MR, Parizotto NA. Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion. Lasers Med Sci. 2012 Aug 17. [Epub ahead of print]

Vatansever F, Hamblin MR. Far infrared radiation (FIR): Its biological effects and medical applications. Photon Laser Med. 2012, in press.

Vatansever F, Rodrigues NC, Assis LL, Peviani SS, Durigan JL,. Moreira FA, Hamblin MR Parizotto NA. Low intensity laser therapy accelerates muscle regeneration in aged rats. Photon Laser Med. 2012, in press.

Assis L, Moretti AI, Abrahão TB, Cury V, Souza HP, Hamblin MR, Parizotto NA. Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion.  Lasers Surg Med. 2012 Sep 21. doi: 10.1002/lsm.22077.

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