Table 1.
PBM1 application on animal sample
| Authors | Animal (sex, age, model) | Total sample size / groups (n) | Behavioral method | Behavioral results | Brain results | PBM parameters (Wavelength nm / Wavelength type (frequency)/ intensity/ irradiance) | Brain target area | Days / Anesthesia |
|---|---|---|---|---|---|---|---|---|
| Buendía et al. (2022) | Mouse (male, 9 months, AD2 model) | N = 23 / Control (n = 5); Control PBM (n = 7); AD control (n = 4); AD PBM (n = 7) |
Recognition memory (Novel Object Recognition test) Locomotor activity (Open field) |
PBM did not improve recognition memory in an AD model PBM did not alter locomotor activity in an AD model |
PBM rescued fEPSP3, LTP4 and partially restored LTD5 in an AD model, while no differences were found in PPF6 | 630 nm/ NR7/ NR/ 1 W | Generalized in a box | 5 consecutive days/ No anesthesia |
| Cardoso et al. (2021) a | Rat (male, 4 and 20 months, healthy) | N = 30/ Young control (n = 8); Young PBM (n = 7); Aged control (n = 7); Aged PBM (n = 8) | – | – |
PBM reversed high concentration of several metabolic pathways in aged rats in the cortex (aspartate, glutamate, ammonia recycling, urea cycle, purine, arginine, proline, alanine, phenylalanine, tyrosine, glutathione metabolism, phosphatidylcholine biosynthesis, glycine and serine) PBM increased concentration of acetate and guanosive tryphosphate in aged rats in the hippocampus |
810 nm/ Continuos /15 J/ 100 mW | 5 irradiation points (coordinates: 1 = AP + 4.20 mm and ML 0.00 m; 2 = AP –5.52 mm and ML + 6.60 MM; 3 = AP –3.00 mm and ML + 6.60 mm; 4 = AP 0.00 mm and ML 0.00 mm; 5 = AP -5.52 mm and ML 0.00 mm) | 58 consecutive days/ No anesthesia |
| Cardoso et al. (2021) b | Rat (male, 4 and 20 months, healthy) | N = 64/ Young control (n = 15); Young PBM (n = 15); Aged control (n = 16); Aged PBM (n = 18) |
Spatial memory (Barnes maze). Associative memory (Inhibitory Avoidance). Anxiety (Elevated Plus Maze). Locomotor activity (Open field test) |
PBM improved spatial memory in aged rats No differences were found in associative memory, anxiety, and locomotor activity |
PBM reduced the cortical expression of IL-58 and increased IL-69, IL–1010, and TNF-α11 in aged rats PBM reduced the hippocampal expression of IP-1012 and fractalkine in aged rats |
810 nm/ Continuous / 15 J/ 100 mW | 5 irradiation points (coordinates: 1 = AP + 4.20 mm and ML 0.00 m; 2 = AP –5.52 mm and ML + 6.60 MM; 3 = AP –3.00 mm and ML + 6.60 mm; 4 = AP 0.00 mm and ML 0.00 mm; 5 = AP –5.52 mm and ML 0.00 mm) | 58 consecutive days/ No anesthesia |
| Cardoso et al. (2021) c | Rat (male, 20 months, healthy) | N = 11 / Aged control (n = 5); Aged PBM (n = 6) | – | – |
PBM increased the cortical expression of STAT313, ERK14, and JNK15, while no differences were found in Akt16, p70S6K17, STAT518, and p38, in aged rats PBM increased the hippocampal expression of p70S6K, STAT3 and Akt, while no differences in STAT5, ERK, JNK and p38 |
810 nm/ Continuous / 15 J/ 100 mW | 5 irradiation points (coordinates: 1 = AP + 4.20 mm and ML 0.00 m; 2 = AP –5.52 mm and ML + 6.60 MM; 3 = AP –3.00 mm and ML + 6.60 mm; 4 = AP 0.00 mm and ML 0.00 mm; 5 = AP –5.52 mm and ML 0.00 mm) | 58 consecutive days/ No anesthesia |
| Cardoso et al. (2022) a | Rat (male, 3 and 20 months, healthy) | N = 24/ Young control (n = 7); Young PBM (n = 5); Aged control (n = 6); Aged PBM (n = 6) | – | – |
PBM increased the CCO19 activity in the ventral basal thalamic nucleus–lateral, caudal caudate–putamen, and nucleus of cranial nerve 3, CA1 of the hippocampus, mammillothalamic tract, auditory cortex, and primary and secondary visual cortex in aged rats PBM reduced the CCO activity of anterodorsal thalamic nucleus in aged rats |
810 nm/ Continuous / 15 J/ 100 mW | 5 irradiation points (coordinates: 1 = AP + 4.20 mm and ML 0.00 m; 2 = AP -5.52 mm and ML + 6.60 MM; 3 = AP –3.00 mm and ML + 6.60 mm; 4 = AP 0.00 mm and ML 0.00 mm; 5 = AP –5.52 mm and ML 0.00 mm) | 58 consecutive days/ No anesthesia |
| Cardoso et al., (2022) b | Rat (male, 20 months, healthy) | N = 10/ Aged control (n = 5); Aged PBM (n = 5) | – | – |
PBM reduced the cortical expression of ERK and p38 and increased the activation of STAT3 and ERK PBM increased the hippocampal expression of p70S6K and STAT5 and reduced the expression of p38 PBM decreased cortical levels of IL–5, and hippocampal levels of IL–5, IL–1820 and fractalkine levels, while increments in IL–1α21 both in the hippocampus and cortex |
660 nm/ Continuous / 15 J/ 100 mW | 5 irradiation points (coordinates: 1 = AP + 4.20 mm and ML 0.00 m; 2 = AP –5.52 mm and ML + 6.60 MM; 3 = AP –3.00 mm and ML + 6.60 mm; 4 = AP 0.00 mm and ML 0.00 mm; 5 = AP –5.52 mm and ML 0.00 mm) | 10 consecutive days/ No anesthesia |
| Cho et al. (2018) | Mouse (male, early intervention started at 2 months and delayed intervention started at 6 months of age, AD model) | NR/ AD PBM early intervention (n = 8–12); AD PBM delayed intervention (n = 8–12); AD control (n = 8–12) | Spatial memory (MWM22). Associative memory (Passive avoidance test). Anxiety (Elevated plus maze test) |
PBM improved spatial memory in an AD model, and reduced anxiety phenotype No differences were found in associative memory |
PBM with early intervention showed a reduction in Aβ plaques, microgliosis, and increased degradation of Aβ proteins and insulin–degrading enzyme in the cortex of an AD model, while no differences were found with delayed interventions, or in the hippocampus | 610 nm/ NR/ 2 J/cm2 / 1.7 mW | 2 irradiation points (midpoint of the parietal bone and the posterior midline of the seventh cervical vertebra) |
48 non–consecutive days (3 times per week)/ Anesthesia |
| De Taboada et al. (2011) | Mouse (male, 3 until 9 months, AD model) | N = 100/ AD control (n = 20); AD continuous PBM (n = 20); AD pulsed PBM 40 mW (n = 20); AD pulsed PBM 200 mW (n = 20); AD pulsed PBM 400 mW (n = 20) | Spatial memory (MWM) | PBM continuous and pulsed (40, 200, and 400 mW) improved spatial memory in an AD model |
PBM reduced Aβ plaques. While there was an increase of sAβPPα protein levels Only pulsed wave at 400 mW and 200 mW decreases amyloid load in the cerebrospinal fluid PBM with NIR leads to a reduction in inflammatory markers, a restored of ATP23 levels and an increase in c-fos protein expression in AD model |
808 nm/ Continuous and pulsed (100 Hz)/ NR/ 40 mW, 200 mW, 400 mW | 1 irradiation point (midline of the skull, 4 mm caudal to the coronal suture) |
72 non-consecutive days (3 times per week)/ Anesthesia |
| El Massri et al. (2018) | Mouse (male, 3 and 12 months, healthy) | N = 16/ Young control (n = 5); Aged control (n = 6); Aged PBM (n = 5) | - | - | PBM reduces astrocytes and microglia in the striatum. No differences were found in pavalbumin and encephalopsin interneurons, nor in striatal dopaminergic terminals | 670 nm/ NR/ NR/ NR | NR | 8 consecutive months/ NR |
| Grillo et al. (2013) | Mouse (female, tested at 3, 7, and 12 months, AD model) | NR / AD control (n = 3–4); AD PBM (n = 3–4) | – | – |
PBM reduced APP24, β–amyloid, and alpha–b-c8rystalin in the hippocampus in AD model PBM upregulated members of the heat shock protein signaling pathways in AD model |
1072 nm/ Pulsed (600 Hz)/ NR/ 5 mW | 6 irradiation points (enclosing the animals, irradiating in all directions from all 6 sides) |
40 non–consecutive days (2 times per week)/ No Anesthesia |
| Hosseini et al. (2022) | Mouse (male, NR, an aging–induced protocol) | N = 50 / Control (n = 10); Aged control (n = 10); Aged PBM 8 J (n = 10); Aged PBM 16 J (n = 10) Aged PBM 32 J (n = 10) | Spatial memory (Lashley III maze). Asociative memory (Passive avoidance test). Sociability (Three–chamber social interaction test) |
PBM with 8 and 16 J/cm2 improved spatial memory in aging–induced mice, and social memory with 8 J/cm2 No differences were found in associative memory, and social interaction, or with 32 J/cm2 |
PBM with 8 and 16 J/cm2 increased GAP–4325 and SYN26 expression in the hippocampus in aging-induced mice, while no effects were found in PSD–9527, or with 32 J/cm2 PBM with 8 and 16 J/cm2 reduced IL–6 hippocampal expression and 8 J/cm2 reduced TNF– α |
810 nm/ Pulsed (10 Hz)/ 8, 16 and 32 J/ 4.75 W/cm2 |
1 irradiation point (approximately bregma) |
24 non–consecutive days (3 times per week)/ No Anesthesia |
| Li et al. (2023) | Mouse (male, 4 until 6 months, AD model) | NR/ AD control (n = 3–10); AD PBM 16 J/cm2 (n = 3–10); AD PBM 32 J/cm2 (n = 3–10) |
Spatial memory memory (MWM) Recognition memory (Novel object recognition test) |
PBM with 32 J/cm2 improved spatial memory and memory recognition in an AD model, but not with 16 J/cm2 |
PBM significantly reduced density of Aβ plaque and the reduction was similar between prefrontal cortex and hippocampus PBM mitigated Aβ burden in the brain by improving lymphatic clearance of Aβ and increased diameter of the basal MLVs28 |
1267 nm/ NR/ 16 and 32 J/cm2 / NR |
1 irradiation point (sagittal sinus region) |
7 non–consecutive days (once every two days)/ Anesthesia |
| Lutfy et al. (2024) a |
Rats (male, 2 months and 16 months, SD29) |
N = 48/ Young control (n = 8); Aged control (n = 8); Young SD (n = 8); Aged SD (n = 8); Young SD PBM (n = 8); Aged SD PBM (n = 8) |
Short–term memory (Y–Maze) Anxiety (Elevated plus maze test) |
PBM did not improved short-term memory in a SD aged model PBM reduced anxiety phenotype |
PBM up–regulated Bcl-2 and BDNF30 in the hippocampus in aged SD, reversed Ach31, AchE32, MAD33, and SOD34 expression, while no differences were found in GSH35 or hippocampal histoarchitecture | 830 nm/ Continuous / 71.96 J/ 100 mW |
6 irradiation points (sagittal on each side of the longitudinal commissure and between bregma and lambda) |
3 consecutive days/ No anesthesia |
| Lutfy et al. (2024) b | Rats (male, 2 months and 16 months, SD.) | N = 48/ Young control (n = 8); Old control (n = 8); Young SD (n = 8); Old SD (n = 8); Young SD PBM (n = 8); Old SD PBM (n = 8) | – | - | PBM increased hypothalamic CCO activity, BDNF and Bax in aged SD, reversed GSH, SOD activity, and histological features, reduced TNF–α, IL–6 and CRP36, while no differences were found in MDA37 | 830 nm/ Continuous / 71.96 J/ 100 mW |
6 irradiation points (on two sides of the animal head) |
3 consecutive days/ No anesthesia |
| Mohammed et al. (2023) |
Rats (male, NR, PD38 model) |
N = 21/ Control (n = 7); PD control (n = 7); PD PBM (n = 7) |
Locomotor activity (Open field) |
PBM restored locomotor activity |
PBM decreased MDA, NO39 and GSH for midbrain and striatum PBM recovered AchE, and monoaminoxidase enzymatic activity in midbrain, while no effects were found in Na + , K + –ATPase. PBM restored 5–HT40 and NE41 levels in the midbrain and striatum while no significant differences were found in DA42 |
830 nm/ Continuous / 71.96 J/ 100 mW | 6 irradiation points (three on each side of the longitudinal commissure and between bregma and lambda) | 14 consecutive days/ No anesthesia |
| Oueslati et al. (2015) | Rat (female, NR, PD model) |
First evaluation: N = 35/ Control (n = 5); PBM 5 mW/cm2 (n = 6); PBM 10 mW/cm2 (n = 6); PBM 20 mW/cm2 (n = 6); PBM 25 mW/cm2 (n = 6); PBM 30 mW/cm2 (n = 6) Second evaluation: N = 23/ PBM 5 mW/cm2 (n = 7) and a PBM 2.5 mW/cm2 (n = 7); Control (n = 9) |
Locomotor activity (Cylinder test) | PBM with 2.5, 5 and 10 mW/cm2 improved locomotor activity (akinesia) | PBM groups showed less nigral dopaminergic degeneration, with a significant protection against α–syn-induced toxicity only on the higher fluence group as well as less striatal fiber denervation with a significant effect observed after treatment at higher fluence. No differences were found in cell survival or cortical cell density | 808 nm/ NR/ NR/ 2.5, 5, 10, 15, 20, 25, 30 mW/cm2 | Above the head | 14 consecutive days + 6 weeks treatment withdrawal + 8 consecutive days/ No anesthesia |
| Salehpour et al. (2017) | Mouse (male, NR, artificially aging-induced protocol) | N = 72/ Control (n = 12); Aged control (n = 12); Aged PBM 660 nm 4 J/cm2 (n = 12); Aged PBM 810 nm 4 J/cm2 (n = 12); Aged PBM 660 nm 8 J/cm2 (n = 12); Aged PBM 810 nm 8 J/cm2 (n = 12) |
Spatial memory (Barnes maze) Episodic memory (What-where-which task) |
PBM with red and NIR and 8 J/cm2 improved spatial memory and episodic-like memory in aging induced mice No differences were found with 4 J/cm2 |
Red and NIR PBM with 8 J/cm2 augmented active mitochondria, MMP43, ATP, and CCO activity while no differences were found with 4 J/cm2 Red and NIR PBM with 4 and 8 J/cm2 reduced ROS44 production There was a significant reduction of Bax to Bcl–2 ratio, and caspase-3 with 8 J/cm2 Red and NIR 8 J/cm2 lasers notably drop caspase11357_2024_12313 protein levels |
660 and 810/ Pulsed (10 Hz)/ 4 and 8 J/cm2/ 200 mW | Above the head |
18 non–consecutive days (3 times per week)/ No Anesthesia |
| Salehpour et al. (2018) | Mouse (male, 2 months and 18 months, healthy) | N = 45 / Young control (n = 15); Aged control (n = 15); Aged PBM (n = 15) |
Spatial memory (Barnes Maze) Locomotor activity (Open field test) |
PBM improved spatial memory in aged rats No differences were found in locomotor activity |
PBM increased ATP in the hippocampus | 660 nm/ Continuous/ 16 J/cm2/ 200 mW |
1 irradiation point (3 mm rostral to a line drawn through the anterior base of the ears) |
14 consecutive days/ No anesthesia |
| Shen et al. (2020) | Mouse (NR, NR, AD model) | NR / AD control (n = 4–14); AD PBM (n = 4–14) | Spatial memory (Y-maze and MWM) | PBM improved learning and memory in an AD model |
PBM reduced Aβ depositions in an AD model in the cortex and hippocampus PBM reduced p-JNK and c-Jun signals around plaques PBM increased MKP745 phosphorylation while inhibited the phosphorylation of JNK346 and PSD-95 and AMPA receptor endocytosis PBM rescued the decrease of dendritic spines in an AD model. PBM increased synaptophysin and MAP-247 in the cortex and hippocampus of an AD model |
635 nm/ NR/ 6 J/cm2/ 8.75 mW | Above the head |
30 consecutive days/ No Anesthesia |
| Sipion et al. (2023) | Mouse (male and female, 1 until 6 months, AD model) | N = 60/ Control (n = 19); PBM 5 mW (n = 20); PBM 470 mW (n = 21) |
Spatial memory (MWM) Short-term spatial memory (Y maze) Recognition memory (Novel object recognition test) |
No differences were found in spatial memory, short-term spatial memory, and memory recognition |
PBM did not altered the numbers of neurons in the prefrontal cortex or the amyloid plaque load PBM had no effect regardless of intensity use |
810 nm/ Pulsed (100 Hz)/ NR/ 5 mW and 470 mW | Above the head | 40 non-consecutive days (2 times per week)/ No anesthesia |
| Tao et al. (2021) | Mouse (female, 4 and 12 months AD model) | N = 40–48 / Control (n = 10–12); AD control (n = 10–12); AD PBM 10 Hz (n = 10–12); AD PBM 40 Hz (n = 10–12) |
Spatial memory (MWM) Recognition memory (Novel object recognition test) |
PBM with 10 Hz improved spatial memory and recognition memory in an AD model, but not with 40 Hz |
PBM with 10 and 40 Hz reduced the number of Aβ plaques in the hippocampus and cortex in an AD model of 12 months PBM with 10 Hz increased the colocalization between microglia and Aβ in the cortex of mice, while no differences were found with astrocytes, and it reduced M1-like microglia |
1070 nm/ Pulsed (10 and 40 Hz)/ 4.5 J/cm2/ 25 mW/cm2 | Generalized in a box | 60 consecutive days/ No anesthesia |
| Xu et al. (2024) | Mouse (NR, 4, 8 and 12 months, AD model) |
N = 40/ 4 months control (n = 5); 4 months continuous PBM 808 nm (n = 5); 4 months pulsed 40 Hz PBM 808 nm (n = 5); 4 months pulsed 40 Hz visible light (n = 5); 8 months control (n = 5); 8 months continuous PBM 808 nm (n = 5); 8 months pulsed 40 Hz PBM 808 nm (n = 5); 8 months pulsed 40 Hz visible light (n = 5); 12 months control (n = 5); 12 months continuous PBM 808 nm (n = 5); 12 months pulsed 40 Hz PBM 808 nm (n = 5); 12 months pulsed 40 Hz visible light (n = 5) |
Spatial memory (MWM) | PBM improved spatial memory with 808 nm (continuous and 40 Hz), and visible light |
PBM reduced Aβ plaques in the old mice but not on the young mice. Plaques amount seemed to be least for mice treated by 808 nm and visible LED in 40 Hz PW48 mode Cerebral amyloid angiopathy was not found in AD model mice from 808 nm 40 Hz group in vivo |
808 or visible / Continuous and pulsed (40 Hz)/ NR/ 50 mW/cm2 | Generalized in a box | 7 consecutive days/ No anesthesia |
| Zhang et al. (2024) | Mouse (male, 18–20 months, PND49) | NR/ Control (n = 6–10); PND (n = 6–10); PND PBM 80 J/cm2 (n = 6–10); PND PBM 160 J/cm2 (n = 6–10) |
Short and long-term spatial memory (Barnes maze). Locomotor activity (Open field test) |
PBM with 80 and 160 J/cm2 improved short and long-term spatial memory, and memory recognition in a PND model. No differences were found in locomotor activity |
PBM decreased ROS and TFN- α PBM upregulated the expression of IRF750, reduce microglia M1 and increase M2 phenotype, upregulated the expression of BDNF, CCO and improved ATP production restoring enzyme activity of complexes I, II, IV It altered the profiles of mRNA in the prefrontal cortex and hippocampus and reversed expression of inflammasome proteins |
810 nm/ Continuous /80 and 160 J/cm2/ 80 mW/cm2 | Above the head | 5 consecutive days/ No anesthesia |
1.PBM = photobiomodulation. 2. AD = Alzheimer’s disease. 3. fEPSP = excitatory field potentials. 4. LTP = long-term potentiation. 5. LTD = long-term depression. 6. PPF = paired-pulse facilitation. 7.NR = not reported. 8. IL-5 = interleukin 5. 9. IL-6 = interleukin 6. 10. IL-10 = interleukin 10. 11. TNF-α = tumor necrosis factor alpha. 12. IP-10 = interferon gamma-induced protein. 10. 13. STAT3 = signal Transducer and Activator of Transcription 3. 14. ERK = extracellular-Signal-Regulated Kinase. 15. JNK = c-Jun N-terminal kinases. 16. Akt = protein kinase B. 17. p70S6K = ribosomal protein S6 kinase beta-1. 18. STAT5 = signal Transducer and Activator of Transcription 5. 19. CCO = cytochrome C oxidase. 20. IL-18 = interleukin 18. 21. 1L-1α = interleukin 1 alpha. 22. MWM = morris Water Maze. 23. ATP = adenosine triphosphate. 24. APP = amyloid precursor protein. 25. GAP-43 = growth-associated protein-43. 26. SYP = synaptophysin. 27. PSD-95 = post-synaptic density-95. 28. MLV = meningeal lymphatic vessels. 29. SD = sleep deprived. 30. BDNF = brain-derived neurotrophic factor. 31. Ach = acetylcholine. 32. AchE = Acetylcholinesterase. 33. MAD = malondialdehyde. 34. SOD = super oxide dismutase. 35. GSH = glutathione. 36. CRP = c-reactive-protein. 37. MDA = measured malondialdehyde. 38. PD = Parkinson’s disease. 39. NO = nitric oxide. 40. 5-HT = serotonine. 41. NE = norepinephrine. 42. DA = dopamine. 43. MMP = mitochondrial membrane potencial. 44. ROS = reactive oxygen species. 45. MKP7 = Mitogen-activated protein kinase phosphatase 7. 46. JNK3 = c-Jun N-terminal Kinase 3. 47. MAP2 = microtubule associated protein-2. 48. PW = pulsed wave. 49.PND = postoperative neurocognitive disorder. 50. IRF7 = interferon regulatory factor 7