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. 2024 Jan 19;14(1):112. doi: 10.3390/jpm14010112

Table 1.

Summary of studies investigating the effect of photobiomodulation in animal models of Parkinson’s disease.

Study Animal Model Design PBM Parameters Outcomes
TRANSCRANIAL PBM
Shaw et al., 2010 [131] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 20)/saline + PBM (n = 20)/MPTP (n = 20)/MPTP + PBM (n = 20). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Four treatments over 30 h (after MPTP).		 Reduced neuronal loss;
Increased TH+ cell numbers in SNc.
Shaw et al., 2012 [140] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 24)/saline + PBM (n = 24)/MPTP (n = 24)/MPTP + PBM (n = 24). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Four treatments over 30 h (after MPTP).		 Reduced c-FOS expression in both acute and chronic models.
Peoples et al., 2012 [138] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 21)/saline + PBM (n = 19)/MPTP (n = 22)/MPTP + PBM (n = 18). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Ten treatments after each MPTP injection
OR
Ten treatments after 3 weeks.		 Increased TH+ cell numbers in SNc for both simultaneous PBM treatment and post-treatment.
Peoples et al., 2012 [139] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 21)/saline + PBM (n = 19)/MPTP (n = 22)/MPTP + PBM (n = 18). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Four treatments 4 days after MPTP (simultaneous treatment model)
OR
Ten treatments over 3 weeks (post-treatment model).		 Increased TH+ cell numbers in the retina for both simultaneous PBM treatment and post-treatment.
Moro et al., 2013 [137] Mouse;
BALB/c males + C57BL/6;
MPTP model.		 Saline (n = 10 + 10)/saline + PBM (n = 10 + 10)/MPTP (n = 10 + 10)/MPTP + PBM (n = 10 + 10). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Two PBM treatments immediately after and 6 h after each MPTP injection over 30 h (total of four PBM treatments).		 ncreased TH+ cells in SNc and improved locomotion for albino (BALB) mice but not for black (C57BL) mice—due to reduced penetration of 670 nm.
Purushothuman et al., 2013 [141] Mouse;
K3 transgenic (overexpression of tau protein).		 Wild type (n = 5)/K3 (n = 5)/K3 + PBM (n = 5). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
One PBM treatment per day, 5 days per week for 4 weeks (total of 20 PBM treatments).		 Increased TH+ cells in SNc;
decreased oxidative stress markers.
Johnstone et al., 2014 [152] Mouse;
BALB/c males;
MPTP model (50, 75 and 100 mg/kg).		 50 mg/kg MPTP (n = 36)/75 mg/kg MPTP (n = 8)/100 mg/kg MPTP (n = 9)/50 mg/kg MPTP + transcranial PBM (n = 12)/75 mg/kg MPTP + transcranial PBM (n = 8)/100 mg/kg MPTP + transcranial PBM (n = 19)/50 mg/kg MPTP + remote PBM (n = 11)/75 mg/kg MPTP + remote PBM (n = 8)/100 mg/kg MPTP + remote PBM (n = 9). 670 nm LED;
Transcranial OR remote;
40 mW/cm2 for 90 s;
Two PBM treatments immediately after and 6 h after each MPTP injection (total of four PBM treatments for 50 mg/kg, six for 75 mg/kg and eight for 100 mg/kg MPTP).		 Increased TH+ cells in 50 mg/kg MPTP treatment (not 75 or 100 mg/kg);
Transcranial treatment appeared superior to remote treatment.
Oueslati et al., 2015 [27] Rat;
Transgenic overexpression of α-synuclein.		 Sham (n = 9)/low PBM (n = 7)/high PBM (n = 7). 808 nm laser;
Transcranial;
(Two spots);
2.5 J and 5 J;
Daily for 28 days.		 Reduced neuronal loss;
Reduced motor impairment;
Improvements lasted for 6 weeks after treatment was discontinued.
Reinhart et al., 2015 [136] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 11)/saline + PBM (n = 11)/MPTP (n = 11)/MPTP + PBM (n = 11). 810 nm LED;
Transcranial;
1.6 mW for 90 s;
Four treatments over 30 h (after MPTP).		 Increased TH+ cells in SNc;
Improved locomotion after each PBM treatment.
El Massri et al., 2016 [135] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 20)/saline + PBM (n = 30)/MPTP (n = 30)/MPTP + PBM (n = 40). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Immediately after and 6 h after two MPTP injections (four PBM treatments)
OR
Immediately after and 6 h after four MPTP injections, separated by 7 days (eight PBM treatments)
OR
Two PBM treatments per day for 8 or 12 days (sixteen PBM treatments).		 Increase in TH+ cells in 8 PBM treatment group and 16 PBM treatment group and after 7 days in the 4 PBM treatment group but not after 2 days;
2 J/cm2 was not effective, while 4 J/cm2 was effective for an increased MPTP dose (100 mg/kg).
Ribeiro et al., 2016 [149] Rat;
Wistar;
6OHDA model.		 6OHDA (n = 20)/6OHDA + LED (n = 20)/6OHDA + laser (n = 20). 672 nm LED;
Right cervical region over carotid artery;
70 mW for 57 s;
daily for 7 days;
OR
630 nm laser;
Right cervical region over carotid artery;
45 mW for 88 s;
Daily for 7 days.		 Increased IL-2, IL-10 and interferon with a laser;
Increased IFN-α with LEDs;
Decreased TNF-α with LEDs and a laser;
Motor condition improved significantly with a laser but not LEDs.
Reinhart et al., 2016 [134] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 9)/saline + PBM (n = 11)/MPTP (n = 9)/MPTP + pre MPTP injection PBM (n = 9)/MPTP + simultaneous MPTP injection PBM (n = 9)/MPTP + post MPTP injection PBM (n = 9)/MPTP + pre + simultaneous MPTP injection PBM (n = 9)/MPTP + post + simultaneous MPTP injection PBM (n = 9)/MPTP + pre + post + simultaneous MPTP injection PBM (n = 9). 670 nm LED;
Transcranial;
40 mW/cm2 for 90 s;
Two PBM treatments per day;
Pre, post and simultaneous MPTP injection had four PBM treatments;
pre + simultaneous and post + simultaneous MPTP injection had eight PBM treatments;
pre + post + simultaneous MPTP injection had twelve PBM treatments.		 Increased TH+ cells in all groups;
Locomotion improved in all groups.
San Miguel 2019 [133] Mouse;
C56BL/6 (head shaved);
MPTP model.		 Saline (n = 8)/MPTP (n = 6)/MPTP + PBM (n = 6). 675 LED;
Transcranial;
50 mW/cm2 for 3 min daily for 7 days.		 Reduced vascular leakage in SNc and the caudate putamen complex.
O’Brien and Austin 2019 [150] Rat; Sprague–Dawley male;
Supranigral LPS injection.		 Vehicle sham/LPS sham/LPS + PBM. 670 nm LED array;
Transcranial;
4 J/cm2 twice daily for 6 days.
INTRACRANIAL PBM
Moro et al., 2014 [183] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 5)/saline + continuous PBM (n = 5)/ saline + pulsed PBM (n = 5)/MPTP + continuous PBM (n = 5)/MPTP + pulsed PBM (n = 5). 670 nm LED;
Implanted intracranially;
1.5 mW/cm2 (pulsed) for 90 s per day for 4 days;
14.5 mW/cm2 (continuous) for 6 days continuously.		 Pulsed group showed increased TH+ cells in SNc;
Continuous group showed non-significant increase in TH+ cells in SNc.
Moro et al., 2016 [146] Monkey (macaque);
Adult male;
MPTP model.		 Control (n = 3)/MPTP (n = 5)/MPTP + PBM (n = 7). 670 nm laser;
Implanted intracranially;
10 mW on for 5 s/off for 30 s;
Continuous for 25 days.		 Increased TH+ cells but no increased effect of increased dose compared to Darlot et al. [147].
Reinhart et al., 2016 [142] Rat;
Wistar;
6OHDA model.		 Saline (n = 8)/6OHDA (n = 15)/6OHDA + PBM (pulsed) (n = 16)/6OHDA + PBM (continuous) (n = 13)/6OHDA + PBM (continuous low dose) (n = 9). 670 nm LED
Implanted intracranially;
1.6 mW for 90 s twice daily for 23 days
OR
1.6 mW continuously for 23 days
OR
0.333 mW continuously for 23 days.		 Increased TH+ cells for pulsed group but not continuous groups;
Decreased rotational behaviour for pulsed and high-dose continuous groups but not for low-dose continuous group.
Darlot et al., 2016 [147] Monkey (macaque);
Adult male;
MPTP model.		 Control (n = 5)/1.5 mg/kg MPTP (n = 6)/2.1 mg/kg MPTP (n = 5)/1.5 mg/kg MPTP + PBM (n = 5)/21.1 mg/kg MPTP + PBM (n = 4). 670 nm laser;
Implanted intracranially;
10 mW on for 5 s/off for 30 s;
Continuous for 5 days (1.5 mg/kg MPTP)
OR
Continuous for 7 days (2.1 mg/kg MPTP). 		Increased TH+ cells;
Increased striatal TH+ terminals for lower MPTP group;
Improved clinical scores;
Improved locomotion.
El Massri et al., 2016 [145]

Further results of study from Darlot et al., 2016 [147]		 Monkey (macaque);
Adult male;
MPTP model.		 Control (n = 5)/1.5 mg/kg MPTP (n = 6)/2.1 mg/kg MPTP (n = 5)/1.5 mg/kg MPTP + PBM (n = 5)/21.1 mg/kg MPTP + PBM (n = 4). 670 nm laser;
Implanted intracranially;
10 mW on for 5 s/off for 30 s;
Continuous for 5 days (1.5 mg/kg MPTP)
OR
Continuous for 7 days (2.1 mg/kg MPTP).		 Reduced MPTP-induced astrogliosis in the SNc and striatum.
El Massri et al., 2017 [144]

Further results from studies of Moro et al. [183], Reinhart et al., 2016 [142] and Darlot et al., 2016 [147]		 Mouse;
BABL/c.
+
Rat;
Wistar.
+
Monkey (macaque).

All MPTP models.		 Mouse:
Saline (n = 5)/saline + continuous PBM (n = 5)/saline + pulsed PBM (n = 5)/MPTP + continuous PBM (n = 5)/MPTP + pulsed PBM (n = 5).

Rat:
Saline (n = 8)/6OHDA (n = 15)/6OHDA + PBM (pulsed) (n = 16)/6OHDA + PBM (continuous) (n = 13)/6OHDA + PBM (continuous + low dose) (n = 9).

Monkey:
control (n = 5)/1.5 mg/kg MPTP (n = 6)/2.1 mg/kg MPTP (n = 5)/1.5 mg/kg MPTP + PBM (n = 5)/21.1 mg/kg MPTP + PBM (n = 4).		 670 nm LED;
Implanted intracranially;
Mouse:
1.5 mW/cm2 (pulsed) for 90 s per day for 4 days;
14.5 mW/cm2 (continuous) for 6 days continuously.

Rat:
1.6 mW for 90 s twice daily for 23 days
OR
1.6 mW continuously for 23 days
OR
0.333 mW continuously for 23 days.

Monkey:
10 mW on for 5 s/off for 30 s;
Continuous for 5 days (1.5 mg/kg MPTP)
OR
continuous for 7 days (2.1 mg/kg MPTP).		 Increase in TH+ cells in the striatum of monkeys but not mice or rats;
Increase in glial cell-derived neurotrophic factor (GDNF) in monkeys.
El Massri et al., 2018 [184] Monkey (macaque);
Adult male;
MPTP model.		 Control (n = 3)/control + PBM (n = 3)/MPTP (n = 3)/MPTP + PBM (n = 3). 670 nm laser;
Implanted intracranially;
10 mW on for 5 s/off for 60 s;
Continuous for 5 days.		 No effect on encephalopsin expression in striatum.
REMOTE PBM
Stone et al., 2013 [157] Mouse;
BALB/c males;
MPTP model.		 Saline (n = 5)/saline + PBM (n = 5)/MPTP (n = 5)/MPTP + PBM (n = 5). 670 nm LED;
Remote (body with head shieled);
40 mW/cm2 for 90 s;
Twp PBM treatments immediately after and 6 h after each MPTP injection over 30 h (total of four PBM treatments).		 Increased TH+ cells in SNc.
Wattanathorn and Sutalangka 2014 [148] Rat;
Wistar;
6OHDA model.		 Control (n = 12)/6OHDA (n = 12)/6OHDA sham (n = 12)/6OHDA + PBM (n = 12). 405 nm laser;
Laser acupuncture point HT7;
100 mW for 10 min;
Once daily for 14 days.		 Improved memory; increased cells at CA3 of the hippocampus; decreased markers of oxidative stress.
Johnstone et al., 2014 [152] Mouse;
BALB/c males;
MPTP model (50, 75 and 100 mg/kg).		 50 mg/kg MPTP (n = 36)/75 mg/kg MPTP (n = 8)/100 mg/kg MPTP (n = 9)/50 mg/kg MPTP + transcranial PBM (n = 12)/75 mg/kg MPTP + transcranial PBM (n = 8)/100 mg/kg MPTP + transcranial PBM (n = 19)/50 mg/kg MPTP + remote PBM (n = 11)/75 mg/kg MPTP + remote PBM (n = 8)/100 mg/kg MPTP + remote PBM (n = 9). 670 nm LED;
Transcranial OR remote;
40 mW/cm2 for 90 s;
Two PBM treatments immediately after and 6 h after each MPTP injection (total of four PBM treatments for 50 mg/kg, six for 75 mg/kg and eight for 100 mg/kg MPTP).		 Increased TH+ cells in 50 mg/kg MPTP treatment (not 75 or 100 mg/kg);
Transcranial treatment appeared superior to remote treatment.
Kim et al., 2018 [158] Mouse;
C57BL/6 males;
MPTP model.		 saline (n = 10)/MPTP sham (n = 10)/MPTP + remote ischemic conditioning (leg) (n = 10)/MPTP + PBM (n = 10)/MPTP + remote ischemic conditioning + PBM (n = 10). 670 nm LED;
Remote (dorsum);
50 mW/cm2 for 3 min;
Pre-conditioned prior to MPTP injection.		 Increased TH+ cells with remote ischemic conditioning and remote PBM; no additional benefit from combining treatments.
Ganeshan et al., 2019 [132] Mouse;
BABL/c males;
MPTP model.		 Saline (n = 10)/MPTP (n = 10)/MPTP + PBM 2 days pretreatment (n = 10)/ MPTP + PBM 5 days pre-treatment (n = 10)/MPTP + PBM 10 days pre-treatment (n = 10). 670 nm LED;
Remote (dorsum + hind limbs);
50 mW/cm2 for 90 s for 2, 5 or 10 days prior to MTPT injection.		 Decreased Fos+ in the caudate putamen complex for all pre-treatment groups;
Increased TH+ cells and upregulated cell signalling, cell migration, oxidative stress response and blood–brain barrier modulation in 10-day pre-treatment group only.
Gordon et al., 2023 [143] Mouse;
C56BL/6 (head, abdomen and hind legs shaved).
+
Monkey (macaque);
Adult male.

All MPTP models.		 Mouse:
Control (n = 10)/MPTP (n = 10)/MPTP + PBM (head) (n = 10)/MPTP + PBM (abdomen) (n = 10)/MPTP + PBM (legs) (n = 10).
Monkey:
head (n = 1)/abdomen (n = 1)/hind legs (n = 1).		 Mouse:
656 nm LED;
Transcranial and remote (abdomen + hind legs);
50 mW/cm2 for 180 s;
After MPTP injection, daily for 21 days.
Monkey:
670 nm LED;
Transcranial and remote (abdomen + lower legs);
50 mW/cm2 for 180 s;
Immediately after and 4 h after MPTP injection over 5 days (10 treatments).		 Mouse:
No difference in mobility;
Increased TH+ cells in SNc in all groups.
Monkey (single individual):
Lower clinical score for abdomen and leg treatment.
WHOLE ANIMAL PBM
Vos et al., 2013 [151] Drosophila;
pink1 null mutants;
park null mutants;
Rotenone toxin.		 Variable numbers of mutant pink1 flies/pink1 controls/mutant park flies/park controls. 808 nm laser;
Whole animal;
25 mW/cm2 for 100 s;
Single dose.		 Increased flight times; reduced mitochondrial defects and function; increased mitochondrial (complex IV) respiration.

PBM = photobiomodulation; LED = light emitting diode; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.