Table 2.
Published in vivo studies on the neuroprotection effects of photobiomodulation in neuronal activities
| Study/Year | Relevance | Light Source | Wavelengths | Irradiation parameters | Irradiation approach/sites | Findings |
|---|---|---|---|---|---|---|
| Michalikova et al. 2008 [14] | Naïve middle-age mouse | Laser | 1072 nm | 6 min/day for 10 days | Full body irradiation | Enhanced acquisition of working memory for spatial navigation; no effects on exploratory activity or anxiety responses |
| Uozumi et al. 2010 [121] | Naïve mouse | Laser, B&W Tek, Inc. (Newark, DE, USA) | 808 nm | 0.8, 1.6, or 3.2 W/cm2, spot diameter of 3 mm, 45 min, one irradiation session, CW | Transcranially; At the left hemisphere, 2 mm posterior to and 3 mm left of the bregma |
At 1.6 W/cm2: Increased CBF in the irradiated and opposite hemisphere over the 45 min irradiation; increased cortical NO concentration; decreased neuronal apoptosis induced by transient cerebral ischemia in cerebral cortex and CA1 subfield of dorsal hippocampus |
| Rojas et al. 2012 [17] | Naïve rat | LEDs, LEDtronics, Inc. (Torrance, CA, USA) | 660 nm | 9 mW/cm2, 1, 5, 5.4, 10.9, 21.6, or 32.9 J/cm2; with corresponding duration of 111, 565, 600, 1200, 2400, or 4800 sec, respectively; CW | Transcranially; Holding probe at the 1 cm from the dorsal head surface |
Enhanced O2 consumption in PFC (at 5.4 J/cm2); improved extinction of fear-conditioned memories (at 10.9 J/cm2); decreased renewal of conditioned-fear (at 5.4 J/cm2); increased CCO activity in PFC (at 10.9 J/cm2) |
| Mintzopoulos et al. 2017 [115] | Naïve dog | Laser, PhotoThera, Inc. (Carlsbad, CA, USA) | 808 nm | 4–10 mW/cm2 on the dura mater, 0.48–1.2 J/cm2 per site (total of 2 sites); spot diameter of 22 mm, 2 min, 1 session or 3×/week for 2 weeks, CW | Transcranially; At the anterior and posterior cranium midline locations |
Improved cerebral bioenergetics via increase of PCr/β-NTP ratios and PCr level (at 2 weeks post-irradiation) |
| De Taboada et al. 2011 [9] | AD (mouse APP transgenic model) |
Laser, Photothera, Inc. (Carlsbad, CA, USA) | 808 nm | 1.2, 6, or 12 J/cm2 at cortex; fiber diameter of 3 mm, 2 min, 3×/week for 6 months, PW at 100-Hz with 2 msec pulse duration, or CW | Transcranially; At a point in sagittal suture, 4 mm caudal to coronal suture |
Improved learning and memory in MWM test (by all regimens); decreased CSF (by PW regimens), plasma (by all regimens), and brain (by all regimens) Aβ level; decreased brain inflammatory markers such as IL-1β, TNF-α, and TGF-β (by all regimens); increased ATP level and O2 consumption (by PW at 6 J/cm2) |
| Grillo et al. 2013 [49] | AD (mouse TASTPM model) |
LEDs, Virulite Distribution Limited | 1072 nm | 5 mW/cm2, 1.8 J/cm2, 6 min/day for 2 days, biweekly for 5 months, PW at 600-Hz with DC of 300 μs | Full body irradiation | Increased HSP27, 60, 70, 105 and P-HSP27, and decreased PS1, αB-crystallin, APP, Aβ1–40, Aβ1–42, and phosphorylated tau proteins expression; decreased small Aβ1–40/42 and Aβ1–42plaque deposition in Dentate Gyrus and cerebral cortex |
| Sutalangka et al. 2013 [138] | AD (rat AF64A model) |
Laser, Xinland International Limited (Xi’an, Shaanxi, China) | 405 nm | 52.63 J/cm2, spot diameter of 500 μm, 10 min/day for 2 weeks, CW | Remote tissue irradiation; At the HT7 point or a point 2–4 mm lateral to the HT7 acupoint |
Improved learning and memory in MWM test; increased catalase and SOD activities and decreased AChE activity in hippocampus |
| Purushothu man et al. 2014 [21] | AD (mouse K3 and APP/PS1 transgenic models) |
LEDs, WARP 10; Quantum Devices (Barneveld, WI, USA) | 670 nm | 4 J/cm2, 90 sec, 5×/week for 4 weeks, CW | Transcranially; Holding probe 1 to 2 cm above the head |
K3 mouse: decreased phosphorylated tau and NFTs in neocortex and hippocampus; decreased oxidative stress markers such as 8-OHDG and 4-HNE in neocortex; enhanced CCO expression patterns in neocortex and hippocampus APP/PS1 mouse: decreased number, size, and burden of Aβ plaques in neocortex and hippocampus |
| Farfara et al. 2015 [191] | AD (mouse 5XFAD transgenic model) |
NR | NR | 400 mW, 1 J/cm2, spot diameter of 0.3 cm, 6× (at 10-day intervals, for 2 months), CW | Remote tissue irradiation; At the middle portion of the medial part of the tibia |
Improved memory in object recognition and fear-conditioning tests; decreased Aβ burden in hippocampus |
| Purushothu man et al. 2015 [236] | AD (mouse K3 and APP/PS1 transgenic models) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 4 J/cm2, 90 sec, 5×/week for 4 weeks, CW | Transcranially; Holding probe 1 to 2 cm above the head |
APP/PS1 mouse: reduced number, size and deposition of Aβ plaques in cerebellar cortex K3 mouse: decreased formation of NFTs, phosphorylated tau, oxidative stress, and increased CCO expression in cerebellar cortex |
| Da Luz Eltchechem et al. 2017 [237] | AD (rat Aβ25–35 model) |
LEDs, AlGalnP, RL5-R12008 | 627 nm | 70 mW, 7 J/cm2, 100 sec/day for 21 days | Transcranially; Holding probe at 1 cm from the frontal region of scalp |
Improved motor skills in OFT at days 14 and 21; improved spatial memory in MWM test at day 14; reduced amount of Aβ |
| Lu et al. 2017 [20] | AD (rat Aβ1–42 model) |
Laser, 808M100, Dragon Lasers (Changchun, China) |
808 nm | 25 mW/cm2, 3 J/cm2 at cerebral cortex, spot area of 1 cm2, 2 min/day for 5 consecutive days, CW | Transcranially; At the 3 mm posterior to eye and 2 mm anterior to ear |
Suppressed neuronal degeneration; suppressed expression of mitochondrial fission and preserved mitochondrial fusion proteins; recovered changes in mitochondrial dynamics; improved mitochondrial function through reduction of Bax/Bcl-2 ratio and increase of MMP, CCO activity and ATP levels; inhibited G6PDH and NADPH oxidase activities; enhanced total antioxidant capacity; inhibited glial activation, proinflammatory cytokines production and tau hyperphosphorylation; attenuated cytosolic level of cytochrome c, caspase-9 and-3 activities; improved spatial learning and memory in Barnes maze task and long-term recognition memory in NOR test |
| Shaw et al. 2010 [238] | PD (mouse MPTP model) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 40 mW/cm2 at scalp, 5.3 mW/cm2 inside skull, 0.47 J/cm2 per irradiation (total of 4 irradiations over 30 h), 90 sec, irradiation area of 10 cm2, CW | Transcranially; Holding probe at 1 cm from the head |
Increased TH+ cell numbers in SNc (at 50 and 100 mg/kg MPTP) |
| Peoples et al. 2012 [239] | PD (mouse MPTP model) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 5 J/cm2 over 10 sessions, 90 sec/session, CW | Transcranially; Holding probe at 1–2 cm from the head |
Increased TH+ cell numbers in SNc (at both simultaneous irradiation and post-irradiation regimens) |
| Shaw et al. 2012 [240] | PD (mouse MPTP model) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 0.5 J/cm2, 90 sec, CW | Transcranially; Holding probe at 1–2 cm from the head |
Decreased Fos+ cell numbers in STN and ZI after acute (~1 day) and chronic (5 weeks) MPTP insult |
| Moro et al. 2013 [241] | PD (MPTP Balb/c and C57BL/6 mouse models) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 0.47 J/cm2 per session (total of 4 sessions over 30 h), 90 sec, CW | Transcranially; Holding probe at 1–2 cm from the head |
Balb/c mouse: increased TH+ cell numbers in SNc; improved locomotor activities in OFT including velocity, high mobility and immobility times |
| Johnstone et al. 2014 [67] | PD (mouse MPTP models) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 40 mW/cm2, 4 J/cm2, 90 sec, CW | Head or body irradiation | At both head or body irradiations: increased TH+ cell numbers in SNc (at 50 mg/kg MPTP); increased glial cell numbers in SNc (at 75 mg/kg MPTP) |
| Moro et al. 2014 [68] | PD (mouse MPTP models) |
LEDs, (SMT 670, Epitex) coupled with an optical fiber (FT300EMT, Thorlabs) | 670 nm | 1.5 mW/cm2 (PW) or 14.5 mW/cm2 (CW), fiber diameter of 300 μm, continuous irradiation for 6 days | Intracranially; Implant site: lateral ventricle |
Increased TH+ cell numbers in SNc (at PW mode); no observable behavioral and tissue deficits |
| Oueslati et al. 2015 [10] | PD (rat AAV-based genetic model) |
Laser, RLTMDL-808–2W, Roithner Lasertechnik GmbH (Vienna, Austria) | 808 nm | 2.5 or 5 mW/cm2 at midbrain, 2 irradiation spots of about 1 cm2, 100 sec/day for 4 weeks | Transcranially; Irradiation of both sides of the head |
Improved motor performance in cylinder test (at 2.5 or 5 mW/cm2); decreased dopaminergic neuronal loss in the substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum (at 5 mW/cm2) |
| Reinhart et al. 2015 [242] | PD (mouse MPTP models) |
LEDs, LED EPITEX SMT810, EPITEX Inc. (Kyoto, Japan) | 810 nm | 160 mW, 57.6 mJ (at skull for total of 4 irradiations), 90 sec/session | Transcranially; Full head irradiation |
Increased TH+ cell numbers in SNc; improved locomotor activity in OFT |
| Darlot et al. 2016 [64] | PD (monkey MPTP model) |
Laser, coupled with an optical fiber (HCP-MO200T) | 670 nm | 10 mW; 25 or 35 J over 5 or 7 days, respectively; with 5 seconds ON/60 seconds OFF | Intracranially; Implant site: 4 mm rostral to posterior commissure, 3 mm below anterior commissure-posterior commissure line |
Improved PD signs and locomotor activities including movement and velocity; increased number of nigral Nissl-stained and TH+ cells and striatal TH+ terminals; no observable behavioral and tissue deficits |
| Massri et al. 2016 [243] | PD (monkey MPTP model) |
Laser, coupled with an optical fiber (HCP-MO200T) | 670 nm | 10 mW; 25 or 35 J over 7 days; with 5 seconds ON/60 seconds OFF | Intracranially; Implant site: near the SNc of both sides |
Decreased number and cell size of astrocytes in both the SNc and striatum; decreased cell size of microglia in both the SNc and striatum |
| Moro et al. 2016 [244] | PD (monkey MPTP model) |
Laser, coupled with an optical fiber (HCP-MO200T) | 670 nm | 10 mW, 125 J for 25 days continuous irradiation, with 5 seconds ON/60 seconds OFF | Intracranially; Implant site: a region close to midline in the midbrain, encompassing the ventral tegmental area |
Improved PD signs; increased number of nigral Nissl-stained cells and density of striatal TH+ terminals |
| Reinhart et al. 2016 [245] | PD (rat 6-OHDA model) |
LEDs, (SMT 670; Epitex) coupled with an optical fiber (FT300EMT; Thorlabs) | 670 nm | 333 nW or 0.16 mW, 634 mJ or 304 J, fiber diameter of 300 μm, for 23 consecutive days, PW (2×/day for 90 sec) or CW | Intracranially; Implant site: a region near the SNc (including red nucleus and ventral tegmental area) |
Decreased rotational behavior at days 14 (at CW of 304 J) and 21 (at CW of 304 J, and PW of 634 mJ); increased TH+ cell numbers in SNc (at PW of 634 mJ) |
| Reinhart et al. 2016 [246] | PD (mouse MPTP model) |
LEDs, WARP 10, Quantum Devices (Barneveld, WI, USA) | 670 nm | 5.3 mW/cm2, ~0.5 J/cm2 at midbrain, 90 sec, 2×/day for 2, 4, or 6 days, CW | Transcranially; Holding probe at 1–2 cm from the head |
Improved locomotor activity in OFT (at all regimens); increased TH+ cell numbers in SNc (at all regimens) |
| Reinhart et al. 2016 [247] | PD (mouse MPTP model) |
LEDs, Epitex devices (models 670-66-60 and 810-66-60; epoxy lens infrared illuminators) | 670 and/or 810 nm | 15 or 30 mW, total dosage of 11 or 22 J, 45 or 90 sec, 2×/day for 2 days, CW | Transcranially; Full head irradiation |
Improved locomotor activity in OFT and increased TH+ cell numbers in SNc (at all regimens, especially in concurrent and sequential irradiation regimens) |
| Massri et al. 2017 [169] | PD (mouse and monkey MPTP model, and rat 6-OHDA model) |
Laser, coupled with an optical fiber | 670 nm | 0.16 mW for mouse and rat, and 10 mW for monkey, fiber diameter of 300 μm, continuous irradiation for 2 (mouse), 23 (rat) and 5 (monkey) days | Intracranially; Implant sites: lateral ventricle in mouse, a midline region of midbrain in rat and monkey |
Increased number of TH+ cells, TH+ terminal density, and GDNF expression patterns in striatum of monkey |
| Leung et al. 2002 [137] | Stroke (rat cerebral ischemia model) |
Laser, Omega Excel Laser (London, UK) |
660 nm | 8.8 mW, 2.64, 13.2, or 26.4 J/cm2; with corresponding duration of 1, 5, or 10 min, respectively; one irradiation session, PW at 10-Hz | Transcutaneously; Directly through a burr hole 5 mm from the cerebrum |
Decreased specific activity of NOS and increased expression of TGF-β1 at 4 days post-injury (at all regimens); down-regulated expression of three NOS isoforms including eNOS, nNOS, and iNOS at 4 days post-injury (at all regimens) |
| Lapchak et al. 2004 [6] | Stroke (rabbit embolic model) |
Laser, Acculaser (PhotoThera, Inc) coupled with OZ Optics Ltd fiber | 808 nm | 7 mW/cm2 for 2 min (0.84 J/cm2) or 25 mW/cm2 for 10 min (15 J/cm2), one irradiation session, CW | Transcranially; Holding probe in direct contact with the skin |
Improved behavioral performance and decreased effective clot dose for stroke 3 h after clot injection (at cortical fluence of 15 J/cm2) |
| De Taboada et al. 2006 [248] | Stroke (rat atherothrombotic model) |
Laser, GaAs, Photothera, Inc. (San Diego, CA, USA) | 808 nm | 7.5 mW/cm2 at brain tissue level, 0.9 J/cm2 per site (total of 2 sites), fiber diameter of 4 mm, 2 min, one irradiation session | Transcranially; At two locations on head (3 mm dorsal to eye and 2 mm anterior to ear) either ipsilateral, contralateral, or to both sides of stroke |
Improved modified neurological score at 14, 21, and 28 days post-stroke (by all irradiated locations in the skull) |
| Oron et al. 2006 [170] | Stroke (rat atherothrombotic model) |
Laser, GaAs (PhotoThera, Inc) | 808 nm | 7.5 mW/cm2 at brain tissue level, 0.9 J/cm2 per site (total of 2 sites), fiber diameter of 4 mm, 2 min, PW at 70-Hz or CW | Transcranially; At two locations on head (3 mm dorsal to eye and 2 mm anterior to ear) and on contralateral hemisphere to stroke |
Improved neurological scores at 14 and 21 days post-stroke (CW mode when applied 24 h post-stroke); increased SVZ cell proliferation and migration (CW mode) |
| Lapchak et al. 2007 [228] | Stroke (rabbit embolic model) |
Laser, Acculaser coupled with OZ Optics Ltd fiber optic (Berkeley, CA, USA) | 808 nm | 7.5 mW/cm2, 0.9–1.2 J, 2 min, PW at 100-Hz (2 msec pulse duration with DC of 20%) or 1000-Hz (0.3 msec pulse duration with DC of 30%), or CW | Transcranially; Holding probe in direct contact with shaved scalp |
Improved behavioral performance and decreased effective clot dose for stroke 6 h after clot injection (at both PW mode regimens) |
| Lapchak et al. 2008 [249] | Stroke (rabbit embolic model) |
Laser, Acculaser coupled with OZ Optics Ltd fiber optic | 808 nm | 10 mW/cm2, 2 min, one irradiation session, CW | Transcranially; Holding probe in direct contact with scalp |
No significant effects on hemorrhage incidence, volume or survival rate |
| Lapchak et al. 2010 [111] | Stroke (rabbit embolic model) |
Laser, Acculaser coupled with OZ Optics Ltd fiber optic | 808 nm | 7.5, 37.5, or 262.5 mW/cm2; 0.9, 4.5, or 31.5 J/cm2 at cortex, spot diameter of 5 mm, 2 min, PW at 100-Hz or CW | Transcranially; Holding probe in direct contact with scalp |
Increased cortical ATP content (at PW mode, both of 4.5 and 31.5 J/cm2) |
| Yip et al. 2011 [8] | Stroke (rat cerebral ischemia model) |
Laser, GaAlAs, Omega Excel Laser (London, UK) | 606 nm | 8.8 mW, 2.64, 13.20, or 26.40 J/cm2; with corresponding duration of 1, 5, or 10 min, respectively; PW at 10-Hz | Transcutaneously; Directly through a burr hole 5 mm from the cerebrum |
Increased expression of Akt, phosphorylated-Akt, Bcl-2 and pBAD (at all regimens); decreased expression of caspase-3 (at all regimens) and caspase-9 (at 2.64 and 13.20 J/cm2) at 4 days post-stroke |
| Choi et al. 2012 [145] | Stroke (rat focal cerebral ischemia and reperfusion model) |
LEDs, Qray Inc. (Seongnam, Korea) | 710 nm | 0.042 mW/cm2, 1.796 J/cm2, irradiation area of 1.13 cm2, 12 h/day continuous irradiation for 20 days | Full body irradiation; Randomly over the whole skin |
Increased CD4+ (after 2 and 10 days post-stroke) and CD8+ T (after 10 and 20 days post-stroke) cell populations; decreased infarct volume (at day 21); increased expression of IL-10 (at day 20); decreased microglial activation in striatum and cortex (at day 20); increased number of CD4+CD25+ Treg cells in ischemic core and penumbra; improved neurological severity score and step fault scores |
| Huisa et al. 2013 [250] | Stroke (rabbit small clot embolic model) |
Laser, Acculaser coupled with OZ Optics Ltd fiber optic | 808.5 nm | 7.5, 10.8, or 20 mW/cm2, 2 min, CW | Transcranially; Holding probe in direct contact with scalp |
Improved behavioral performance and decreased effective clot dose for stroke (at double and triple irradiation regimens) |
| Fukuzaki et al. 2015 [215] | Stroke (mouse transient mild ischemia model) |
Laser, Nd:YVO4, SUWTECH, LDC-2500 (China) | 532 nm | 845 mW/cm2, 30.4 × 102 J/cm2 at cortex, 60 min, CW | Transcranially; At the surface of temporal skull over left auditory cortex |
Promoted the migration of NSPCs into deeper layers of the neocortex; increased phosphorylated-Akt and Akt expression levels at 4 h post-irradiation |
| Lapchak and Boitano 2016 [110] | Stroke (rabbit small clot embolic model) |
Laser, GaAIAs, coupled with OZ Optics Ltd fiber optic cable | 808 nm | 7.5 mW/cm2, 0.9 J/cm2 at cortex, 2 min, CW | Transcranially; Holding probe in direct contact with scalp |
Improved behavioral performance at 2 day post-stroke; increased cortical ATP levels at 6 h post-stroke |
| Lee et al. 2016 [24] | Stroke (mouse photothrombotic cerebral focal ischemia model) |
LEDs, Color Seven Co. (Seoul, Korea) | 610 nm | 1.7 mW/cm2, 2 J/cm2, spot diameter of 4 mm, 20 min, twice a day for 2 days prior to ischemic event, CW | Transcranially; At the skin via double-sided tape at the right midpoint of the parietal bone and the posterior midline of the seventh cervical vertebra |
At 24 h post-stroke: decreased infarct size and edema; improved neurological and motor function; decreased astrocyte and microglia cells; decreased transcription of iNOS, COX-2, TNF-α, IL-1β, TLR-2, CCL2 and CXCL10 in the ischemic cortex; decrease in protein levels of COX-2 and TLR2; inhibited p38, JNK and ERK-1/2 MAPK activation; attenuated translocation of the NF-κB p65 protein subunit from cytosol to nucleus; attenuated MPO protein levels; improved rearrangement of tight junction proteins and attenuated blood-brain barrier disruption |
| Meyer et al. 2016 [226] | Stroke (rabbit small clot embolic model) |
Laser, coupled with OZ Optics Ltd fiber optic cable (PhotoThera, SanDiego, CA, USA) | 808.5 nm | 7.5–333 mW/cm2 at cortex, 2 min, 1 or 3 irradiation sessions, CW or PW at 10- or 100-Hz with DC of 20% | Transcranially; Holding probe in direct contact with shaved skull |
Improved behavioral performance at 2 h post-stroke (at 1,111 mW/cm2 with 100-Hz PW); no observable tissue necrosis or microscopic neural damage |
| Lee et al. 2017 [147] | Stroke (mouse photothrombotic cerebral focal ischemia model) |
LEDs, Color Seven Co. (Seoul, Korea) | 610 nm | 1.7 mW/cm2, 2 J/cm2, spot diameter of 4 mm, 20 min, twice a day for 3 days.. commencing at 4 h post-ischemia, CW | Transcranially; At the skin via double-sided tape at the right midpoint of the parietal bone and the posterior midline of the seventh cervical vertebra |
At 72 h post-stroke: decreased infarct volume; improved neurological function; decreased MPO protein levels as a marker for neutrophil infiltration; decreased microglial activation via decrease of Iba-1(+)/CD68(+) cells; decreased cell death and reduced NLRP3, cleaved caspase-1 and -11, IL-1β and IL-18 levels; decreased TLR-2 protein levels; suppressed phospho-JNK and phospho-ERK; decreased translocation of NF-κB p65 protein subunit into nucleus |
| Lee et al. 2017 [122] | Stroke (mouse middle cerebral artery occlusion/reperfusion model) |
LEDs, Color Seven Co. (Seoul, Korea) | 610 nm | 1.7 mW/cm2, 2 J/cm2, spot diameter of 4 mm, 20 min, twice a day for 2 days prior to ischemic event, CW | Transcranially; At the skin via double-sided tape at the right midpoint of the parietal bone and the posterior midline of the seventh cervical vertebra |
At 24 h post-stroke: decreased infarct size and edema; improved neurological function; improved vestibular-motor dysfunction in WGT; increased CBF during 30 min after reperfusion; increased phosphorylated eNOS and decreased phosphorylated Akt expression levels |
| Yun et al. 2017 [171] | Stroke (rat middle cerebral artery occlusion model) |
Laser, Ellise-005, Ver. 1.0.1, Wontech (Daejeon, South Korea) | 650 nm | 30 mW, fiber diameter of 125 μm, 5 min, once every 2 days for 2 weeks, PW at 100-Hz | Laser acupuncture points; At the GV20 (head) and HT7 (right forepaw) points |
Improved learning and memory in MWM test; decreased cholinergic neuronal cell loss in the hippocampal CA1 region; upregulated gene expression of CREB, BDNF, and Bcl-2 and downregulated gene expression of Bax. |
| Oron et al. 2007 [251] | TBI (mouse) |
Laser, PhotoThera, Inc. (Carlsbad, CA, USA) | 808 nm | 10 or 20 mW/cm2, 1.2 or 2.4 J/cm2, fiber diameter of 3 mm, 2 min, CW | Transcranially; At the sagittal suture located 4 mm caudal to coronal suture |
Improved neurological severity score at 5–28 days post-TBI (at both regimens); decreased lesion volume at 28 days post-TBI (at both regimens) |
| Moreira et al. 2009 [25] | TBI (rat) |
Laser, MM Optics Ltda (São Carlos, SP, Brazil) | 660 or 780 nm | 40 mW, 3 or 5 J/cm2 per site (total of 2 sites); irradiation area of 0.04 cm2, 3 or 5 sec, CW | Direct irradiation; At the injury site |
Brain: decreased IL-1β at 24 h post-TBI compared to 6 h (at 5 J/cm2 660 nm, or 3 J/cm2 780 nm) Blood: increased TNF-α at 24 h vs. 6 h (at 3 J/cm2 660 nm, 5 J/cm2 660 nm, or 5 J/cm2 780 nm); increased IL-6 at 24 h vs. 6 h (at 3 J/cm2 660 nm, 5 J/cm2 660 nm, or 5 J/cm2 780 nm); decreased IL-6 at 6 or 24 h vs. control (at 3 J/cm2 660 nm) |
| Ando et al. 2011 [7] | TBI/post TBI depression (mouse model) |
Laser, DioDent Micro 810, HOYA ConBio (Fremont, CA, USA) | 810 nm | 50 mW/cm2, 36 J/cm2, 12 min, one irradiation session, CW or PW at 10- or 100-Hz with DC of 50% | Transcutaneously; On the left front-parietal cortex (3 mm anterior to lambda and 2.5 mm left of midline) |
Improved neurological severity score and increased body weight (at all regimens); improved depressive-like behaviors at 28 days post-TBI in FST (at 10-Hz) and TST (at 10- and 100-Hz); decreased lesion size at 15 and 28 days post–TBI (at 10-Hz) |
| Khuman et al. 2012 [252] | TBI (mouse) |
Laser, Thor Photomedicine Ltd. (Chesham, Buckinghamshire, UK) |
800 nm | 250–1000 mW/cm2, 60–210 J/cm2, spot area of 1.32 cm2, 2 or 7 min, CW | A) via an open craniotomy; Holding probe at 1 cm above head B) Transcranially; At the right and left parieto-temporal region |
Improved cognitive performance in MWM test (at 60 J/cm2 by transcranially or via an open craniotomy); decreased microglial activation at 48 h post-TBI |
| Quirk et al. 2012 [22] | TBI (rat) |
LEDs | 670 nm | 50 mW/cm2, 15 J/cm2, 5 min, 2 sessions/day for 72 h or 10 days, CW | Transcranially; Holding probe at 0.5 cm above the head |
Improved locomotor activity in OFT (at 10 days post-irradiation); increased Bcl-2 and GSH, and decreased Bax expression levels |
| Wu et al. 2012 [97] | TBI (mouse) |
Laser, BWF-665-1, B&W-Tek; 730/6, Diomed Inc.; DioDent Micro 810 and V-Raser, ConBio (USA) |
665, 730, 810, or 980 nm | 150 mW/cm2, 36 J/cm2, spot diameter of 1 cm, 4 min, one irradiation session, CW | Transcranially; Over the sutured incision |
Improved neurological severity score and decreased small deficits in brain at 4 weeks post-irradiation (at 665 or 810 nm) |
| Xuan et al. 2013 [96] | TBI (mouse) |
Laser, DioDent Micro 810, HOYA ConBio (Fremont, CA, USA) | 810 nm | 25 mW/cm2, 18 J/cm2, spot diameter of 1 cm, 12 min, for 1, 3, or 14 days, CW | Transcranially; Centrally on top of the head |
By 1 or 3×day: improved neurological severity scores and WGT scores; decreased brain lesions sizes at 14 and 28 days post-TBI By 3×day: decreased degeneration at 14 and increased neurogenesis at 28 days post-TBI |
| Xuan et al. 2014 [166] | TBI (mouse) |
Laser, DioDent Micro 810, HOYA ConBio (Fremont, CA, USA) | 810 nm | 25 mW/cm2, 18 J/cm2, spot diameter of 1 cm, 12 min, for 1 or 3 consecutive days, CW | Transcranially; Entire head irradiation |
At both 1 and 3×day: improved motor functions in WGT (at days 21, and 28 post-TBI); improved learning and memory in MWM (at day 28); decreased caspase-3 expression in lesion region (at day 4); increased neurogenesis in Dentate Gyrus and SVZ (at days 7 and 28); up-regulated migrating neuroprogenitor cells and neuronal differentiation in Dentate Gyrus and SVZ (at days 7 and 28) |
| Zhang et al. 2014 [146] | TBI (mouse) |
Laser, Acculaser, PhotoThera (Carlsbad, CA, USA) | 810 nm | 150 mW/cm2, 36 J/cm2, spot diameter of 1 cm, 4 min, PW at 10-Hz (50 msec pulse duration) | Transcranially; Holding probe in direct contact with scalp at contusion site |
Improved neurological severity score and increased body weight gain (at 3–28 days post-TBI); decreased IL-1β (at 6 h) and IL-6, CCL2, and CXCL10 (at 6 h and 28 days); upregulated TNF-α; decreased morphological deficits such as necrotic and apoptotic cells in neocortex and hippocampus (at 28 days); increased cortical ATP (at 6 h and 28 days) |
| Dong et al. 2015 [112] | TBI (mouse) |
Laser, Acculaser, PhotoThera (Carlsbad, CA, USA) | 810 nm | 150 mW/cm2, 36 J/cm2, 4 min, PW at 10-Hz (50 msec pulse duration) | Transcranially; Holding probe in direct contact with scalp at contusion site |
Prevented the loss of hippocampal tissues; protected the hippocampus from secondary damage; increased ATP and deceased ROS production in injured cortex (at 5 h post-TBI); decreased lesion size (at 3 and 7 days) |
| Xuan et al. 2015 [26] | TBI (mouse) |
Laser, PhotoThera, Inc. (Carlsbad, CA, USA) | 810 nm | 50 mW/cm2, 36 J/cm2 at scalp, spot diameter of 1 cm, 12 min, for 1 or 3 days, CW | Transcranially | At 1×day: improved neurological severity score (at 21 and 28 days post-TBI); increased expression of BDNF in Dentate Gyrus and SVZ By 3×day: improved neurological severity score (at 14, 21 and 28 days); increased expression of BDNF in Dentate Gyrus and SVZ area, and synapsin-1 in SVZ and lesion area (at 28 days) |
| Xuan et al. 2016 [28] | TBI (mouse) |
Laser, DioDent Micro 810, HOYA ConBio (Fremont, CA, USA) | 810 nm | 25 mW/cm2, 18 J/cm2, spot diameter of 1 cm, 12 min, for 3 or 14 days, CW | Transcranially; Covered the entire skull |
By 3×day: improved neurological severity score; improved cognitive performance in MWM test; decreased lesion size (at 2–8 weeks post-TBI); increased expression of GFAP in perilesional cortex, Dentate Gyrus and SVZ (at 8 weeks) By 14×day: decreased lesion size (at 8 weeks); increased expression of GFAP in perilesional cortex, Dentate Gyrus and SVZ (at 8 weeks) |
| Wu et al. 2012 [227] | Depression (rat chronic stress model) |
Laser, PhotoThera, Inc. (Carlsbad, CA, USA) | 810 nm | 350 mW, 120 J/cm2, probe diameter of 3 mm, 2 min, 3×/week for 3 weeks, PW at 100-Hz with DC of 20% | Transcranially; At the midline of the dorsal surface of the shaved head in region between eyes and ears |
decreased depressive-like behaviors in FST |
| Mohammed 2016 [253] | Depression (rat pharmacological model) | Laser, Lasotronic Inc. (Zug, Switzerland) | 804 nm | 640 mW/cm2, 38 J/cm2 per point, spot diameter of 4 mm, 1 min per point, for 7 consecutive days, CW | Transcranially; At six points arranged symmetrically, three on each side of the skull |
Decreased depressive-like behaviors in FST; regulated EEG in all wave frequency bands such as Delta, Alpha, Beta-1, and Beta-2 except for theta wave |
| Salehpour et al. 2016 [85] | Depression (rat chronic stress model) |
Laser, Mustang 2000+ (Moscow, Russia) | 630 or 810 nm | 89 or 562 mW/cm2; 6 or 10.7 J/cm2; probe diameter of 3 mm, 4×/week for 3 weeks, PW at 10-Hz with DC of 50% | Transcranially; At the midline of the dorsal surface of the shaved scalp in prefrontal region |
810 nm: decreased depressive-like behaviors in FST; increased body weight; decreased blood glucose levels 630 nm: decreased serum cortisol and blood glucose levels |
| Xu et al. 2016 [29] | Depression (mouse space restriction or Ahi1 KO model) |
Laser, quartz-silica fiber, Shenzhen Fuzhe Technology Co., Ltd. (Shenzhen, China) | 808 nm | 23 mW/cm2, 41.4 J/cm2, spot diameter of 1 cm, 30 min/day for 28 consecutive days, CW | Transcranially | Stress mouse: decreased depressive-like behaviors in FST and TST (at days 14, 21, and 28); increased ATP synthesis in PFC, increased CCO levels and activity in PFC Ahi1 KO mouse: decreased depressive-like behaviors in FST and TST (at day 28) |
| Salehpour et al. 2017 [13] | Aging (mouse D-galactose model) | Laser, Thor Photomedicine (Chesham, UK) | 660 or 810 nm | 200 mW, 4.75 W/cm2, 4 or 8 J/cm2, 3×/week for 6 weeks, PW at 10-Hz with DC of 88% | Transcranially; Covered the entire brain |
660 and 810 nm: improved spatial memory in Barnes maze test and episodic-like memory in What-Where-Which test (at 8 J/cm2); increased number of vital mitochondria, ATP content, MMP and CCO activity (at 8 J/cm2); decreased ROS levels (at 4 and 8 J/cm2); attenuated apoptosis via decrease of Bax/Bcl-2 and caspase-3 levels (at 8 J/cm2) |
Note: 4-HNE, 4-Hydroxynonenal; PS1, presenilin-1; 6-OHDA, 6-hydroxydopamine; 8-OHDG, 8-hydroxydeoxyguanosine; Aβ, amyloid beta; AChE, acetylcholinesterase; AD, Alzheimer’s disease; Akt, Protein kinase B; APP, amyloid precursor protein; ATP, adenosine triphosphate; β-nucleoside triphosphate; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; BDNF, brain-derived neurotrophic; CBF, cerebral blood flow; CCL2, C-C motif chemokine Ligand 2; CCO, cytochrome c oxidase; CD, cluster of differentiation; COX-2, cyclooxygenase 2; CREB, cAMP responsive element binding; CSF, cerebrospinal fluid; CW, continuous wave; CXCL10, C-X-C motif chemokine 10; DC, duty cycle; EEG, electroencephalography; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal-regulated kinases; FST, forced swimming test; G6PDH, glucose-6-phosphate dehydrogenase; GaAs, gallium arsenide; GaAlAs, gallium aluminum arsenide; GDNF, glial-cell-line-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; GSH, glutathione; HSP, heat shock protein; Iba-1, ionized calcium binding adaptor molecule 1; IL, interleukin; iNOS, inducible nitric oxide synthase; JNK, Jun kinases; KO, knockout; LEDs, light emitting diodes; MAPK, mitogen-activated protein kinases; MMP, mitochondrial membrane potential; MPO, myeloperoxidase; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MWM, Morris water maze; NADPH, nicotinamide adenine dinucleotide phosphate hydrogen; NF-κB, nuclear factor kappa B; NFTs, neurofibrillary tangles; NLRP3, pyrin domain-containing 3; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; NOR, novel object recognition; NOS, nitric oxide synthase; NR, not reported; NSPCs, neural stem/precursor cells; OFT, open field test; pBAD, phosphorylated Bcl-2-associated death promoter; PCr, phosphocreatine; β-NTP; PD, Parkinson’s disease; PFC, prefrontal cortex; P-HSP, phosphorylated heat shock protein; PW, pulsed wave; ROS, reactive oxygen species; SNc, substantia nigra pars compacta; SOD, superoxide dismutase; SVZ, subventricular zone; TBI, traumatic brain injury; TGF-β, Transforming growth factor–β; TH, tyrosine hydroxylase; TLR-2, Toll-like receptor 2; TNF-α, tumor necrosis factor-α; TST, tail suspension test; WGT, wire-grip test