Table 1.
Published in vitro studies on the neuroprotection effects of photobiomodulation in neuronal activities
| Study/Year | Cell types | Light Source | Wavelengths | Irradiation parameters | Findings |
|---|---|---|---|---|---|
| Oron et al. 2007 [113] | Cultured human neuronal cells | Laser, GaAs, Photothera, Inc. (Carlsbad, CA, USA) | 808 nm | 600 mW, 50 mW/cm2, 0.05 J/cm2, 1 sec | Increased ATP content at 10 min post-irradiation |
| Sharma et al. 2011 [2] | Cultured mouse cortical neurons | Laser, Photothera, Inc. (Carlsbad, CA, USA) | 810 nm | 25 mW/cm2; 0.03, 0.3, 3, 10, or 30 J/cm2, single irradiation, CW | Highest increase in mitochondrial ROS (at 3 and 30 J/cm2); increased intracellular NO (at 0.3 J/cm2); increased MMP (at 0.3 and 3 J/cm2); increased intracellular Ca2+ (at 3 J/cm2); increased intracellular ATP (at 3 J/cm2) |
| Fukuzaki et al. 2013 [216] | Human-derived glioblastoma cells | Laser, SUWTECH, LDC-2500 (China) | 532 nm | 60 mW, 845 mW/cm2, 10.1, 20.3, or 30.4 × 102 J/cm2; with corresponding duration of 20, 40 or 60 min; CW | Increased cell proliferation at 48 h post-irradiation through elevation of Akt expression mediated by suppression of PTEN production (at 20.3 and 30.4 × 102 J/cm2) |
| Fukuzaki et al. 2015 [215] | Neural stem/progenitor cell derived | Laser, SUWTECH, LDC-2500 (China) | 532 nm | 60 mW, 845 mW/cm2, 10.1, 20.3, or 30.4 × 102 J/cm2; with corresponding duration of 20, 40 or 60 min; CW | Increased cell proliferation (at 30.4 × 102 J/cm2); promoted migration of NSPCs through increased Akt expression |
| Yan et al. 2017 [27] | Dorsal root ganglion neurons | Laser, HN-1000, Laser Technology Application Research Institute (Guangzhou, China) | 632.8 nm | 12.74 mW/cm2; 0.5, 1, 1.9, and 3.8 J/cm2; with corresponding duration of 0.7, 1.25, 2.5, and 5 min in the dark, respectively; single irradiation, CW | Enhanced cell viability and neuritogenesis through induction of BDNF mRNA expression by increasing of Ca2+ influx, phosphorylated levels of CREB and ERK proteins |
| Duan et al. 2003 [156] | PC12 cell (Aβ25–35-induced neurotoxicity) |
LEDs, self-made GaAlAs | 640 nm | 0.05–1 mW/cm2, 30–60 min, single irradiation, CW | At 0.09 mW/cm2 and 60 min diminished apoptosis and attenuated DNA fragmentation |
| Yang et al. 2010 [134] | Primary astrocytes (Aβ1–42-induced neurotoxicity) |
Laser, He-Ne | 632.8 nm | 1.5 mW/cm2, 16.2 J/cm2, 3 h, single irradiation, CW | Decreased oxidative stress burden via suppression of superoxide anion production, NADPH oxidase; and phosphorylation of cPLA2; inhibited pro-inflammatory markers including IL-1β and iNOS |
| Sommer et al. 2012 [107] | SH-EP and PC12 cells (Aβ42-induced neurotoxicity) |
Laser | 670 nm | 17.36 mW/cm2, 1 J/cm2, 1 min, single irradiation, PW at 1-Hz | Increased ATP levels in Aβ42-free SH-EP cells SH-EP cells: reduced intracellular Aβ42 aggregate amounts; increased cell proliferation PC12 cells: small decrease in ATP levels in Aβ42-challenged |
| Liang et al. 2012 [165] | SH-SY5Y, PC12, and HEK293T cells (Aβ25–35-induced neurotoxicity) |
Laser, HN-1000 (Guangzhou, China) | 632.8 nm | 12.74 mW/cm2, 2 J/cm2, single irradiation, CW | In all cell types: decreased apoptosis via Akt/GSK3b/b-catenin pathway |
| Meng et al. 2013 [168] | SH-SY5Y cell and mice hippocampal primary neuron (Aβ25–35 and Aβ1–42-induced neurotoxicity) |
Laser, HN-1000, Laser Technology Application Research Institute (Guangzhou, China) | 632.8 nm | 12.74 mW/cm2; 0.5, 1, 2, or 4 J/cm2; with corresponding duration of 0.7, 1.25, 2.5, and 5 min in the dark, respectively; single irradiation, CW | At 2 J/cm2: promoted cell survival and improved dendrite growth atrophy through up-regulation of BDNF mediated by activation of ERK/CREB signaling pathway |
| Duggett and Chazot 2014 [47] | Cath.a-differentiated cells (Aβ1–42-induced neurotoxicity) |
LEDs, Virulite Distribution Ltd (UK) | 1068 nm | 5 mW/cm2, 5 sets of 3 min irradiation (with 30 min interval) for 3 days, PW at 600-Hz, with DC of 300 μ sec | Decreased cell death (3.5–25 μM of Aβ42) |
| Trimmer et al. 2009 [108] | PD cybrid cells | Laser, Acculaser, PhotoThera, Inc. (Carlsbad, CA, USA) | 810 nm | 50 mW/cm2, 2 J/cm2, 40 sec, single irradiation, CW | Increased total distance traveled and velocity of mitochondria at 2 h post-irradiation |
| Wong-Riley et al. 2001 [104] | Cultured rat cortical neurons (TTX-induced neurotoxicity) |
LEDs, GaAlAs | 670 nm | 50 mW/cm2, 4 J/cm2, 80 sec, CW | Increased CCO activity in all three metabolic categories of neurons (daily irradiation for 5 days); increased CCO activity in darkly reactive cell type (a single irradiation) |
| Wong-Riley et al. 2005 [103] | Cultured rat visual cortical neurons (KCN-induced neurotoxicity) |
LEDs, Quantum Devices, Inc. (Barnaveld, WI, USA) | 670, 728, 770, 830, or 880 nm | 50 mW/cm2, 4 to 30 J/cm2, 80 to 600 sec, CW | 670 and 830 nm significantly increased CCO activity and ATP content back to control levels compared to 728, 880, and 770 nm (each at 4 J/cm2) 670 nm: pre-irradiation at 30 J/cm2 reduced cell death |
| Liang et al. 2006 [23] | Cultured rat visual cortical neurons (KCN-induced neurotoxicity) |
LEDs, Quantum Devices, Inc. (Barnaveld, WI, USA) | 670 nm | 50 mW/cm2, 30 J/cm2, single irradiation, CW | Pre-irradiation reduced cell death (100 μM of KCN) and (300 μM of KCN); reduced number of ssDNA-positive neurons (100 μM of KCN) and (300 μM of KCN); reduced caspase-3 and Bax levels, and increased Bcl-2 levels (both 100 and 300 μM of KCN); reduced ROS production (300 μM of KCN) |
| Liang et al. 2008 [135] | Cultured rat occipital cortical and striatal neurons (KCN- or MMP+- or rotenone-induced neurotoxicity) |
LEDs, Quantum Devices, Inc. (Barnaveld, WI, USA) | 670 nm | 50 mW/cm2, 4 J/cm2, 80 sec, 1 to 4×/day, CW | KCN: reduced apoptosis (1 irradiation) and (2 irradiations); reduced ROS production (2, 3, and 4 irradiations); reduced NO production (2 and 3 irradiations); reduced nitrotyrosine expression (2 irradiations); highest increase in CCO activity and ATP level (2 irradiations) MPP+: twice a day irradiation suppressed ROS and NO generation, increased ATP level and attenuated apoptosis in both types of neurons Rotenone: twice a day irradiation reduced apoptosis, ROS and NO levels, and increased ATP level in both types of neurons |
| Ying et al. 2008 [106] | Cultured rat visual cortical and striatal neurons (Rotenone- or MPP+-induced neurotoxicity) |
LEDs, Quantum Devices, Inc. (Barnaveld, WI, USA) | 670 nm | 50 mW/cm2, 4 J/cm2, 80 sec, CW | Rotenone: LED irradiation and pre-irradiation decreased apoptosis in both types of neurons; MPP+: LED irradiation and pre-irradiation decreased apoptosis in both types of neurons; LED irradiation and pre-irradiation increased ATP content in striatal neurons |
| Giuliani et al. 2009 [235] | PC12 cell (H2O2-induced neurotoxicity) |
Laser, SANYO DL3149-055A, (RGM, Genoa, Italy) | 670 nm | 0.005 or 0.011 mW/cm2; 0.11, 0.22, 5.06 or 10.12 J/cm2; 20 or 900 sec, single irradiation, PW at 100-Hz with DC of 1% or 50% | Enhanced axonal protection via stimulation of NGF-induced neurite outgrowth; rescued MMP (at all fluencies); increased cell viability (at 0.11 and 0.22 J/cm2) |
| Huang et al. 2013 [32] | Cultured mouse cortical neurons (H2O2- or CoCl2- or rotenone-induced neurotoxicity) |
Laser, Photothera, Inc. (Carlsbad, CA, USA) | 810 nm | 20 mW/cm2; 3 J/cm2, 150 sec, single irradiation, CW | Increased cell viability (at 10 and 20μM of H2O2, 0.2, 0.5, 1, and 2 mM of CoCl2, and 0.2, 2, and 5 μM of rotenone); decreased mitochondrial and cytoplasmic ROS production, and increased MMP (at 500 μM of CoCl2, 20 μM of H2O2, and 200 nM of rotenone) |
| Dong et al. 2015 [112] | Cultured SH-SY5Y cells (CoCl2-induced neurotoxicity) |
LEDs, PhotoMedex (Horsham, PA, USA) | 830 nm | 0.1, 0.5, 1, 3, or 10 J/cm2, CW | Increased cell viability and ATP production (at 3 and 10 J/cm2); decreased lactate production at 18 h post-toxin treatment (at 3 J/cm2); decreased ROS production and increased MMP; reduced cytochrome c leakage and diminished caspase-3 activation; suppressed apoptosis (at 3 J/cm2) |
| Choi et al. 2012 [213] | Cultured rat cortical neurons (OGD-induced neurotoxicity) |
LEDs, QRAY, Inc. (Seoul, Korea) | 710 nm | 50 mW/cm2, 4 J/cm2, 4 min, 1 to 4× within 8 h at 2 h intervals for 7 days, CW | Enhanced cell protection; promoted neurite outgrowth and synaptogenesis mediated by MAPK activation |
| Yu et al. 2015 [136] | Cultured mouse cortical neurons (OGD-induced neurotoxicity) |
Laser, Photothera, Inc. (Carlsbad, CA, USA) | 810 nm | 25 mW/cm2, 0.3 J/cm2, 2 min, single irradiation, CW | Decreased NO production and nNOS activity (at 5 and 30 min post-irradiation); decreased NO donor SNAP-induced neuron death; promoted Akt and Bcl-2 expression (at 1 and 2 h); ameliorated Bax and BAD expression (at 1 and 2 h); suppressed caspase-3 and cleaved caspase-3 expression (at 2 h) |
Note: Aβ, amyloid beta; Akt, Protein kinase B; ATP, adenosine triphosphate; BAD, Bcl-2-associated death promoter; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; BDNF, brain-derived neurotrophic; CCO, cytochrome c oxidase; cPLA2, cytosolic phospholipase A2; CREB, cAMP responsive element binding; CW, continuous wave; DC, duty cycle; DNA, deoxyribonucleic acid; ERK, extracellular signal-regulated kinase; GaAlAs, gallium aluminum arsenide; GaAs, gallium arsenide; GSK3b, glycogen synthase kinase-3β gene; He-Ne, helium–neon; IL, interleukin; iNOS, inducible nitric oxide; KCN, potassium cyanide; LEDs, light emitting diodes; MAPK, mitogen-activated protein kinase; MMP, mitochondrial membrane potential; MMP+, 1-methyl-4-phenylpyridinium ion; mRNA, messenger ribonucleic acid; NADPH, nicotinamide adenine dinucleotide phosphate; NGF, nerve growth factor; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; NSPCs, neural stem/progenitor cells; OGD, oxygen-glucose deprivation; PD, Parkinson’s disease; PTEN, phosphatase and tensin homolog deleted on chromosome ten; PW, pulsed wave; ROS, reactive oxygen species; SNAP, S-nitro-N-acetylpenicillamine; ssDNA, single-stranded DNA; TTX, tetrodotoxin