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Table 3 Characteristics of the included studies outcomes, light source parameters and combination treatment, in experimental studies

From: Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review

Author

Disease category

Disorder

Species

Sex/Age

Combination therapy

Laser

Treatment duration

Key outcomes

Salehpour et al., 2019 [96]

Neuropsychiatric

Depression

BALB/c mice

M / Adult

CoQ10

810 nm, 33.3 J/cm2, 6.66 W/cm2

5 days

Antidepressant-like effects; Decreased lipid peroxidation, corticosterone, TNF-α, and IL-6;

Enhanced total TAC, GSH levels, GPx and SOD activities in HIP and PFC; The inflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels; Down-regulated intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9

Meynaghizadeh-Zargar et al., 2020 [97]

Neuropsychiatric

Chronic mild stress

BALB/c mice

M / 8 weeks

Methylene blue

810 nm, 8 J/cm2, 4.75 W/cm2

4 weeks

(3/week)

Anxiolytic effects; Therapeutic effects on mitochondrial dysfunction, learning and memory impairments; Decreased serum cortisol levels, NO production, ROS production, SOD; Increased TAC, GPx

Farazi et al., 2022 [98]

Neuropsychiatric

Depression

BALB/c mice

M / Adult

Environmental enrichment

810 nm, 8 J/cm2, 4.75 W/cm2

14 days

Antidepressant-like effects; Up-regulated hippocampal BDNF/TrkB/CREB signaling pathway

Moges et al., 2009 [99]

Neurodegenerative

Amyotrophic lateral sclerosis

G93A SOD1 Transgenic mice

NM / 51 days

Riboflavin

810 nm, 12 J/cm2

(3/week)

The lack of significant improvement in survival and motor performance indicates interventions were ineffective in altering disease progression

Lapchak et al., 2008 [100]

Ischemia

Embolic stroke model

New Zealand white rabbits

M / NM

Tissue plasminogen activator

808 nm, 10 mW/cm2

NM

Near-infrared laser therapy may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume

Li et al., 2014 [101]

Ischemia

Hypoxic-ischemic brain damage

Sprague–Dawley rats

M, F / 3 months

Mesenchymal stem cell

660 nm, 60 mW/cm2

7 days

Diode irradiation promotes migration of the transplanted bone marrow mesenchymal stem cells

Salehpour et al., 2019 [102]

Ischemia

Ischemia

BALB/c mice

M / Adult

CoQ10

810 nm, 33.3 J/cm2, 6.66 W/cm2

14 days

Improved spatial and episodic memory; Lowered ROS levels; Increased ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis including SIRT1, PGC-1α, NRF1, and TFAM; Decreased inflammatory responsiveness, iNOS, TNF-α and IL-1β levels

Menovsky et al., 2003 [103]

Nerve injury

Sciatic nerve crush

Wistar rats

M

Solder and suture materials

CO2 laser

NM

Leads to optimal early histological results and least foreign-body reaction at the repair site

Duke et al., 2012 [104]

Nerve injury

Sciatic nerve crush

Sprague–Dawley rats

M

Electrical stimulation

1875 nm

NM

Reduces the laser power requirements and mitigates the risk of thermal damage while maintaining spatial selectivity

Dias et al., 2013 [105]

Nerve injury

Sciatic nerve crush

Wistar rats

M

Natural latex protein

780 nm, 15 J/cm2, 0.75 W/cm2

6 sessions (Alternate days)

Improved the myelin density and morphological characteristics; The capillary density and ultrastructural characteristics were similar to the control group

Yang et al., 2016 [106]

Nerve injury

Sciatic nerve crush

Sprague–Dawley rats

M / Adult

Mesenchymal stem cells

660 nm, 9 J/cm2

7 days

Provided greater functional recovery; Potentiated recovery in SFI, VA and AA; Increased electrophysiological function and expression of S100 immunoreactivity; Reduced the inflammatory cells

Dias et al., 2015 [107]

Nerve injury

Sciatic nerve crush

Wistar rats

M

Latex protein

780 nm, 15 J/cm2, 0.75 W/cm2

6 sessions (Alternate days)

Improvement of the nerve characteristics including the morphometric and ultrastructural characteristics of nerve fibers

Muniz et al., 2015 [108]

Nerve injury

Sciatic nerve crush

Wistar rats

M

Natural latex protein

780 nm, 15 J/cm2, 0.75 W/cm2

12 days

(6/48 h)

Improved muscle fiber atrophy; Increased light fiber area and reduced dark fiber area

de Souza et al., 2018 [109]

Nerve injury

Sciatic nerve crush

Swiss mice

M / Adult

Dexamethasone

660 nm, 10 J/cm2

28 days

Improved nerve regeneration through the SSI and SFI assessments

Dias et al., 2019 [110]

Nerve injury

Sciatic nerve crush

Wistar rats

M / 2 months

Natural latex protein

780 nm, 15 J/cm2, 0.75 W/cm2

6 sessions (Alternate days)

Improved nerve fiber regeneration; Reduced the number, density, diameter and organization of nerve fibers; Increased NGF, VEGF

de Souza et al., 2021 [111]

Nerve injury

Sciatic nerve crush

Swiss mice

M / 3 months

Simvastatin

660 nm, 10 J/cm2

28 days

Sciatic functional index, thermal heat hyperalgesia, mechanical hyperalgesia, and thermographic were evaluated; The results showed that PBM alone was more effective compared to Simvastatin alone or combination

Souza et al., 2013 [112]

Nerve injury

Spinal cord injury

Wistar rats

M / 20—21 weeks

Monosialoganglioside

NM

42 days

Combination therapy shows no superior functional, neurological or histological results

Janzadeh et al., 2017 [113]

Nerve injury

Spinal cord injury

Wistar rats

M / Adult

Chondroitinase ABC

660 nm, 0.5 J/cm2, 0.819 W/cm2

14 days

Improved motor function recovery, myelination and number of axons; Decreased GSK3β, CSPG, and AQP4 expression

Pedram et al., 2018 [114]

Nerve injury

Spinal cord injury

Fischer-344,

Wistar rats

M / 8 – 12 weeks

Meloxicam

810 nm, 6 J/cm2, 200 mW/cm2

2 weeks

Increased BBB test results;

Histological findings revealed no significant difference between all study groups

Sarveazad et al., 2019 [115]

Nerve injury

Spinal cord injury

Wistar rats

M / Adult

Human adipose derived stem cells

660 nm

2 weeks

Improved the motor function, SCI-induced allodynia and hyperalgesia; Increased the GDNF, GABA receptors and Gad65 expression level; Reduced the expression of GSK3β, IL-6, AQP4

Janzadeh et al., 2020 [116]

Nerve injury

Spinal cord injury

Wistar rats

M / Adult

Chondroitinase ABC

660 nm, 22.8 J/cm2, 500 mW/cm2

2 weeks

Reduced allodynia and thermal hyperalgesia; Improved functional recovery; Did not reduce mechanical hyperalgesia; Decreased BDNF and IL-6; Increased Gad65 and GDNF; Reduced neuropathic pain; Improved movement

Chen et al., 2021 [117]

Nerve injury

Spinal cord injury

Sprague–Dawley rats

M / 12 weeks

Human umbilical cord mesenchymal stem cells

630 nm, 100 mW/cm2

14 days

Improved neurofilament structure and arrangement; Promoted motor function and neuronal recovery; Increased the expression of NF‐200, glial fibrillary acidic protein in the damaged area and the BBB scores; Nissl bodies were more numerous and the nerve fibers were longer and thicker; Reduced lesions volume and secondary damage; Promoted functional recovery

Dong et al., 2015 [118]

Nerve injury

Traumatic brain injury

C57BL/6 mice

NM / 8 weeks

Lactate / Pyruvate

810 nm, 36 J/cm2, 150 mW/cm2

NM

Retained memory and learning activities of injured mice to a normal level; Low levels of glycolysis; Increased ATP; Reduced formation of ROS and apoptosis in neurons

Buchaim et al., 2016 [119]

Nerve injury

Facial nerve injury

Wistar rats

M / 60 days

Heterologous fibrin sealant

830 nm, 6 J/cm2, 258.6 mW/cm2

5 weeks

(3/week)

Combination group presented the closest results to the control, in all nerve morphometry indexes (regeneration), except in the axon area

de Oliveira Rosso et al., 2017 [120]

Nerve injury

Facial nerve injury

Wistar rats

M / 80 days

Heterologous fibrin sealant

830 nm, 6.2 J/cm2, 0.26 W/cm2

5 weeks

(3/week)

A significant difference in the fiber nerve area;

The functional recovery of whisker movement;

Accelerated morphological and functional nerve repair

Jameie et al., 2014 [121]

Pain

Neuropathic pain

(Chronic constriction injury model)

Wistar rat

M / Adult

CoQ10

980 nm, 4 J/cm2, 0.248 W/cm2

2 weeks

Cellular and molecular synergism on pain relief;

Increased thermal and mechanical sense thresholds

Noma et al., 2020 [122]

Pain

Neuropathic pain

(Trigeminal nerve injury)

Sprague–Dawley Wistar rat

M / 5–6 weeks

Oxytocin

810 nm, 0.1 W

3 days

The expanded area of cortical excitation caused by model was suppressed by combination therapy but not by each treatment alone; Combined application is effective in relieving the neuropathic pain

Martins et al., 2020 [123]

Pain

Orofacial pain

Wistar rats

M / 2 months

Vitamins B complex

904 nm, 6 J/cm2

10 sessions

Maximal antiallodynic effect; Improved the nociceptive behavior; Down-regulated expression of GFAP, Iba-1, IL-1β, IL-6 and TNF-α; Increased IL-10 expression

de Freitas Dutra Júnior et al., 2022 [124]

Pain

Calcaneus tendon injury

Wistar rats

NM / 60 days

Heterologous fibrin biopolymer

660 nm, 6 J/cm2, 1 W/cm2

3 weeks

(1/week)

Reduced the volume of the edema; Stimulate the repair process; Tenocyte proliferation, granulation tissue and collagen formation were observed in the PTCT area

  1. AA ankle angle, AQP4 aquaporin 4, ATP adenosine triphosphate, BAX Bcl-2 associated X protein, BBB Basso-Beattie-Bresnahan test, Bcl-2 B-cell lymphoma 2, BDNF brain-derived neurotrophic factor, CoQ10 Coenzyme Q10, CREB cAMP response element-binding, CSPG chondroitin sulfate proteoglycan, F Female, GABA Gamma-aminobutyric acid, Gad65 Glutamic acid decarboxylase65, GDNF glial-derived neurotrophic factor, GFAP glial fibrillary acid protein, GPx glutathione peroxidase, GSH glutathione, GSK3β glycogen synthase kinase-3β, HIP hippocampus, Iba-1 ionized calcium binding adaptor molecule 1, IL-10 Interleukin-10, IL-1β Interleukin-1β, IL-6 interleukin-6, iNOS inducible NO synthase, JNK c-Jun aminoterminal kinases, M Male, NF‐200 neurofilament 200, NF-kB nuclear factor-Kb, NGF nerve growth factor, NM not mentioned, NO nitric oxide, NRF1 nuclear respiratory factor 1, PFC prefrontal cortex, PGC1-α peroxisome proliferator-activated receptor gamma coactivator-1 alpha, PTCT partial transection of the calcaneus tendon, ROS reactive oxygen species, SFI Sciatic Functional Index, SIRT1 silent mating-type information regulation 2 homolog 1, SOD superoxide dismutase, SSI Sciatic Static Index, TAC total antioxidant capacity, TFAM mitochondrial transcription factor A, TNF-α tumor necrosis factor-alpha, tPA tissue plasminogen activator, TrkB tyrosine receptor kinase B, VA vertical activity of locomotion, VEGF vascular endothelium growth factor