Medical Lasers; Engineering, Basic Research, and Clinical Application 2021; 10(3): 132-137  https://doi.org/10.25289/ML.2021.10.3.132
Intranasal Photobiomodulation Therapy for Brain Conditions: A Review
Shin Hyuk Yoo1,2
1Department of Otorhinolaryngology and 2Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Korea
Correspondence to: Shin Hyuk Yoo
Department of Otorhinolaryngology, Dankook University College of Medicine, 201 Manghyangro, Dongnam-gu, Cheonan 31116, Korea
Tel.: +82-41-550-3933
Fax: +82-41-556-1090
E-mail: shyoomd@gmail.com
Received: July 23, 2021; Accepted: August 31, 2021; Published online: September 30, 2021.
© Korean Society for Laser Medicine and Surgery. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The effects of low-level laser irradiation on cells and tissues, known as photobiomodulation therapy (PBMT), are the basis of photomedicine. Several investigations have evaluated the therapeutic effects of PBMT for neuronal regeneration and differentiation in animal models and humans. Recently, intranasal PBMT (iN-PBMT) has shown potential as a treatment method for neurologic disorders. In this review, we have summarized the various modes of iN-PBMT delivery and their application in the treatment of brain disorders.
Keywords: Photobiomodulation; Intranasal; Laser; Low-level lasers
INTRODUCTION

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), is widely used to treat various medical conditions such as pain, inflammation, blood disorders, musculoskeletal conditions, as well as tissue regeneration.1 PBMT has steadily widened the range of applications to the brain diseases: neurotrauma, neurodegenerative diseases, and neuropsychiatric disorders.2,3 Moreover, brain PBMT is an effective therapeutic modality for central nervous system (CNS) disorders.4 Through several studies, it is proven that PBMT can improve cerebral blood flow, metabolic activity, neurogenesis, and neuroprotection by antioxidant and anti-inflammatory pathway activation.5,6

To deliver the laser light in brain PBMT, several approaches were proposed: transcranial,7 intranasal,8 intra-aural,9 and intraoral10 approaches. Among these approaches, intranasal PBMT (iN-PBMT) can overcome the limitations of the PBMT to provide effective irradiation to the brain, especially on the limbic structures and prefrontal areas.11

In this review, we summarized the applicability of different intranasal irradiation approaches: from the nostril-based method to the implanted nasal methods. Evidence for the effectiveness of iN-PBMT for neurological, neurodegenerative, and neuropsychiatric disorders will also be reviewed.

INTRANASAL PHOTOBIOMODULATION THERAPY

From the nostril

The nose serves as a direct pathway to the brain. Thus, nasal administration could be an effective, efficient and non-invasive option for delivering therapeutic materials to the CNS (Fig. 1A).12 Several intranasal portable devices for iN-PBMT through the nostril approach become commercially available. These iN-PBMT devices are both with red and near-infrared (NIR) diodes (600-680 nm and 800-850 nm wavelength).

Figure 1. Various approaches for intranasal photobiomodulation. (A) nostril-based approach or by (B) cribriform plate, (C) frontal sinus, (D) sphenoid sinus.

It is known that iN-PBMT through the nostril approach improves oxygenation and leads to increased adenosine triphosphate levels in various tissues, including the brain. PBMT absorbed by blood leads to partial photochemical dissociation of hemoglobin ligand complexes such as oxygen, carbon dioxide, nitric oxide (NO).13-15 As a result of light-induced photodissociation of oxyhemoglobin, decreased in arterial oxygen saturation (SpO2) in blood capillary vessels followed by significant enrichment of local tissue oxygenation occurs.16,17 With 660 nm wavelength photons, the laser irradiation effect can be amplified in lymphocytes.18 In addition, releasing small amounts of the NO, vasodilation and perfusion can be increased. Thus, oxygen delivery to tissues can be improved. Thus, nostril-based iN-PBMT could be an effective and attractive modality for treatment of neurodegenerative, neuropsychiatric diseases, and ischemic brain injury.19 Nostril-based iN-PBMT could also modulate NO release from the endothelium and platelets, and can improve cerebrovascular circulation.

Several studies demonstrated that direct tissue exposure to red/NIR light can reduce the influx of polymorphonuclear leukocytes into a targeted site of inflammation, thus decreasing the oxidative burst.20,21 The remote neuroprotective action of iN-PBMT through the nostril approach could be related to modulation of reactive oxygen species (ROS) formation.22 The role of ROS is critical for reprogramming of macrophage polarization to M2 phenotype, and M2 macrophage releases anti-inflammatory mediators which are related to tissue recovery.23 In previous reports, 810 nm wavelength PBMT changed the macrophage polarization to an M2 phenotype and increased level of anti-inflammatory cytokines (interleukin (IL)-4, 13),24 but suppressed pro-inflammatory IL-625 resulting in alternative macrophage activation.

In addition, several other possible pathways were pro- posed that could mediate iN-PBMT: affecting the olfactory nerve, bulb, and endothelium, the autonomic nervous system, and the lymphatic system.26

From the nasal submucosal space and nasal cavity

As abovementioned, the nostril approach through portable devices only provides a negligible amount of light energy into the deep brain structures.11 Thus, recently, implantable iN-PBMT devices were developed to overcome these limitations. With a simple procedure, miniature light-emitting diodes (LEDs) can be implanted into the submucosal pockets in accessible areas of the nose.

The olfactory epithelium is an epithelial tissue layer in the nasal cavity. It is defined by the cribriform plate, which separates the nasal cavity from the brain. As it is close to the cribriform plate, it is proposed as possible and effective implant location for iN-PBMT device. If the implantable light device is located at the cribriform plate, the ventromedial cortex (PFC) and the olfactory bulb could be effectively irraidated (Fig. 1B). Intranasal delivery of red/NIR light can illuminate anteromedial and posteromedial portions of the orbitofrontal cortex (OFC). In addition, when the light source is positioned proximal to the cribriform plate, deposition of the energy on the ventromedial PFC is 658- and 46-fold greater than when the light source is implanted in the nostril or the middle of the nose, respectively.11 In addition, comparing with the dorsolateral PFC, the light source positioned in the cribriform plate led a higher light influence on the ventromedial PFC and OFC. In addition, limbic structures (amygdala and hippocampus) receive only negligible energy from a light source from the nostril, both the cribriform plate and the mid-nose locations can allow a higher deposition of light.11

PFC and OFC can be also effectively irradiated when the implantable light device is inserted at the frontal sinus (Fig. 1C).

From the sphenoid sinus

In the sphenoid sinus, an implantable optical fiber can be positioned (Fig. 1D). For instance, the tip of the optical fiber connected to a LED sourcecan be placed as an indwelling device through endoscopic visualization in the sphenoid sinus.27 However, this requires a surgical procedure to place the device in a fragile bone structure. The sphenoidal sinus lies adjacent to important limbic system structures such as the pituitary gland, amygdala, hypothalamus, and hippocampus. The amygdala is located anterior to the hippocampus and medially in the temporal lobes.The amygdala resides lateral to and somewhat posterior to the sphenoid sinus. In general, the amygdala processes emotional responses (perception of facial expression, anxiety, fear, memory, aggression, decision making).28 Adjacent to the pituitary gland on either side of the third ventricle and above/posterior to the sphenoid sinus, the hippocampus is located. It is involved in the regulation of endocrine, body temperature, food water intake, reproduction and sexual behavior, circadian rhythms, fatigue, emotional responses, and memory function. The hippocampus is a convex structure composed of gray matter tissue inside the para-hippocampal gyrus. It mediates several higher cognitive functions (e.g., learning, long-term memory, spatial navigation, regulation of hypothalamic functions, and emotions).29

The sphenoid sinus could be used as a proper location of an implanted light source. It could provide therapeutic amounts of light to the limbic structures (Fig. 1D). A study made an effort to experimentally examine the light delivery and photon distribution from a transsphenoidal approach, in order to achieve sufficient irradiation of the pars compacta of substantia nigra (SN) in a human cadaver.10 In this study, authors coupled an optical fiber-based light diffuser to a laser diode emitting different wavelengths of 671 or 808 nm, and then the probe was placed in the sphenoidal sinus towards the pars compacta of SN under endoscopic guidance. In compacta of SN, about 0.36% of 808 nm wavelength and 0.03% of 671nm wavelength light emitted by the optical fiber could be reached. When sufficient power was used, these delivered light could provide a sufficient poststimulatory fluence to the SN. In motor planning, movement and reward-seeking, the SN plays an important role.

With transsphenoidal illumination, a reasonable fraction of the light energy could be deposited in the amygdala, hypothalamus, hippocampus, and pituitary gland, before reaching the SN.

INTRANASAL PHOTOBIOMODULATION THERAPY FOR BRAIN CONDITIONS

Neurodegenerative disorders

In one recent study, rapid reversal of cognitive decline and olfactory dysfunction in a mild cognitive impairment (MCI) patient after PBMT via transcranial and intranasal approach was reported.2 Cognitive enhancement was observed by improvements in executive function/visuospatial ability, mathematical ability, and orientation. Working memory and attention also showed significant improvements in the patient.

In addition, some researchers have reported the potential neurotherapeutic role of iN-PBMT for Alzheimer’s disease (AD) and Parkinson’s disease (PD). In a recent case series, 3-months of transcranial plus intranasal PBMT significantly enhanced cognitive performance in patients with mild to moderately severe dementia.8 With a wearable transcranial device, an intranasal LED applicator (810 nm wavelength) was applied providing a 13.8 J/cm2 to the nasal cavity. Besides the improvement in cognitive abilities as assessed by the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale (ADAS-cog), increased sleep quality and decreased levels of anxiety, anger outbursts, and wandering were also observed. In a recent study, Vielight Neuro Gamma device (Vielight Inc., Canada) was used in four patients diagnosed with dementia or AD.30 With a transcranial headset device, the intranasal LED applicator (810 nm wavelength, 40-Hz pulse wave, 15 J/cm2) was applied to the nasal cavity for 3 days/week for 12 weeks at home. Cognitive and behavioral functions were improved according to the neuropsychiatric inventory scores and the ADA-cog score. With multimodality PBMT, cerebral perfusion and connectivity between the lateral parietal nodes in the default-mode network (DMN) and the posterior cingulate cortex.

Some researchers have tested the therapeutic role of iN-PBMT for PD patients.31,32

Traumatic/ischemic brain injury

In a randomized, double-blind, sham-controlled pilot trial study in eight veterans with mild-TBI, combined application of the transcranial LED helmet and intranasal LED applicator for 2 days/week for 8 weeks, resulted in significant improvements in attention and executive function as well as sleep quality at 1-week post-treatment.33

In one study, intranasal intranasal laser irradiation (10 days, 30 minutes, 650 nm, 8.38 mW/cm2) showed improvement of aggregation of red blood cells, plasma viscosity of blood, and lipid profiles.34

Neuropsychiatric disorders and insomnia

Recently, long-term PBMT showed the overall therapeutic effect in a patient with major depression and anxiety.35 For the first 22 months, single-modality iN-PBMT (810 nm LED) was applied to both nostrils providing a 10.65 J/cm2 per nostril. With the progressive increase of the frequency of iN-PBMT sessions, the anxiety symptoms showed regression with about a 3-fold reduction in Anxiety Symptoms Questionnaire Scores. However, iN-PBMT alone did not improve the depressive symptoms until an additional trancranial laser irradiation to the forehead. According to their speculation, the systemic effects of iN-PBMT via the blood cells possibly contributed to the observed anxiolytic effect.

There is also proof of the therapeutic application of PBMT in sleep disorders. Red-light irradiation (658 nm, 30 J/cm2) for two weeks using a whole body treatment machine has been shown to improve sleep quality and serum melatonin levels.36 In studies of the application of t-PBMT in TBI patients, improvement in sleep was reported by many of the patients.37,38 A combined transcranial and intranasal PBMT also resulted in better sleep in patients diagnosed with AD and TBI.8,33 According to a previous report, sleepiness is a common side-effect following the use of 10-Hz intranasal portable devices, inducing brain alpha wave (8-12 Hz), while also producing neuronal stimulation.2 Although mechanisms of action involved in PBMT for sleep improvement are still unknown, modulation of circadian rhythms via an increase in serum melatonin levels36,39 and stimulation of systemic homeostatic response via the blood circulatory system40 were proposed as possible mechanisms.

CONCLUSIONS

Table 1 summarizes the results of some clinical studies on the effects of iN-PBMT on various brain conditions. While iN-PBMT through nostrils for wellness is available, its efficacy and effectiveness is still unproven. Submucosal and frontal iN-PBMT has potential as a novel therapeutic modality, however, there are no aviailable device is in the market. Other approaches through the deeper nose (cribriform plate or sphenoid sinus), iN-PBMT is not yet available with current technology. However, iN-PBMT, using LED applicators, has potential as a novel approach for neurorehabilitation. Thus, more future studies comparing sham, and transcranial PBMT are also warranted.

Table 1 . Intranasal photobiomodulation therapy (PBMT) for brain conditions

ApplicationStudy designIntranasal PBMT conditionReferences
Neurodegenerative disordersMild cognitive impairmentCase report810 nm wavelength 10-Hz pulsed waveSalehpour et al.2
DementiaCase series810 nm wavelength 10-Hz pulsed waveSaltmarche et al.8
Case series810 nm wavelength 10-Hz pulsed waveChao30
Parkinson's diseaseProspective proof-of-concept study810nm wavelength 50-Hz pulsed waveLiebert et al.32
Traumatic/ischemic brain injuryMild traumatic brain injuryRandomized, double-blind, sham-controlled pilot trial study810 nm wavelength 10-Hz pulsed waveBogdanova et al.33
Cerebral infarctionRandomized, double-blind, placebo-controlled study650 nm wavelengthLiu et al.34
Neuropsychiatric disordersMajor depression, anxietyCase report810 nm wavelength 10-Hz pulsed waveCaldieraro et al.35

INTRANASAL PHOTOBIOMODULATION THERAPY

From the nostril

The nose serves as a direct pathway to the brain. Thus, nasal administration could be an effective, efficient and non-invasive option for delivering therapeutic materials to the CNS (Fig. 1A).12 Several intranasal portable devices for iN-PBMT through the nostril approach become commercially available. These iN-PBMT devices are both with red and near-infrared (NIR) diodes (600-680 nm and 800-850 nm wavelength).

Figure 1. Various approaches for intranasal photobiomodulation. (A) nostril-based approach or by (B) cribriform plate, (C) frontal sinus, (D) sphenoid sinus.

It is known that iN-PBMT through the nostril approach improves oxygenation and leads to increased adenosine triphosphate levels in various tissues, including the brain. PBMT absorbed by blood leads to partial photochemical dissociation of hemoglobin ligand complexes such as oxygen, carbon dioxide, nitric oxide (NO).13-15 As a result of light-induced photodissociation of oxyhemoglobin, decreased in arterial oxygen saturation (SpO2) in blood capillary vessels followed by significant enrichment of local tissue oxygenation occurs.16,17 With 660 nm wavelength photons, the laser irradiation effect can be amplified in lymphocytes.18 In addition, releasing small amounts of the NO, vasodilation and perfusion can be increased. Thus, oxygen delivery to tissues can be improved. Thus, nostril-based iN-PBMT could be an effective and attractive modality for treatment of neurodegenerative, neuropsychiatric diseases, and ischemic brain injury.19 Nostril-based iN-PBMT could also modulate NO release from the endothelium and platelets, and can improve cerebrovascular circulation.

Several studies demonstrated that direct tissue exposure to red/NIR light can reduce the influx of polymorphonuclear leukocytes into a targeted site of inflammation, thus decreasing the oxidative burst.20,21 The remote neuroprotective action of iN-PBMT through the nostril approach could be related to modulation of reactive oxygen species (ROS) formation.22 The role of ROS is critical for reprogramming of macrophage polarization to M2 phenotype, and M2 macrophage releases anti-inflammatory mediators which are related to tissue recovery.23 In previous reports, 810 nm wavelength PBMT changed the macrophage polarization to an M2 phenotype and increased level of anti-inflammatory cytokines (interleukin (IL)-4, 13),24 but suppressed pro-inflammatory IL-625 resulting in alternative macrophage activation.

In addition, several other possible pathways were pro- posed that could mediate iN-PBMT: affecting the olfactory nerve, bulb, and endothelium, the autonomic nervous system, and the lymphatic system.26

From the nasal submucosal space and nasal cavity

As abovementioned, the nostril approach through portable devices only provides a negligible amount of light energy into the deep brain structures.11 Thus, recently, implantable iN-PBMT devices were developed to overcome these limitations. With a simple procedure, miniature light-emitting diodes (LEDs) can be implanted into the submucosal pockets in accessible areas of the nose.

The olfactory epithelium is an epithelial tissue layer in the nasal cavity. It is defined by the cribriform plate, which separates the nasal cavity from the brain. As it is close to the cribriform plate, it is proposed as possible and effective implant location for iN-PBMT device. If the implantable light device is located at the cribriform plate, the ventromedial cortex (PFC) and the olfactory bulb could be effectively irraidated (Fig. 1B). Intranasal delivery of red/NIR light can illuminate anteromedial and posteromedial portions of the orbitofrontal cortex (OFC). In addition, when the light source is positioned proximal to the cribriform plate, deposition of the energy on the ventromedial PFC is 658- and 46-fold greater than when the light source is implanted in the nostril or the middle of the nose, respectively.11 In addition, comparing with the dorsolateral PFC, the light source positioned in the cribriform plate led a higher light influence on the ventromedial PFC and OFC. In addition, limbic structures (amygdala and hippocampus) receive only negligible energy from a light source from the nostril, both the cribriform plate and the mid-nose locations can allow a higher deposition of light.11

PFC and OFC can be also effectively irradiated when the implantable light device is inserted at the frontal sinus (Fig. 1C).

From the sphenoid sinus

In the sphenoid sinus, an implantable optical fiber can be positioned (Fig. 1D). For instance, the tip of the optical fiber connected to a LED sourcecan be placed as an indwelling device through endoscopic visualization in the sphenoid sinus.27 However, this requires a surgical procedure to place the device in a fragile bone structure. The sphenoidal sinus lies adjacent to important limbic system structures such as the pituitary gland, amygdala, hypothalamus, and hippocampus. The amygdala is located anterior to the hippocampus and medially in the temporal lobes.The amygdala resides lateral to and somewhat posterior to the sphenoid sinus. In general, the amygdala processes emotional responses (perception of facial expression, anxiety, fear, memory, aggression, decision making).28 Adjacent to the pituitary gland on either side of the third ventricle and above/posterior to the sphenoid sinus, the hippocampus is located. It is involved in the regulation of endocrine, body temperature, food water intake, reproduction and sexual behavior, circadian rhythms, fatigue, emotional responses, and memory function. The hippocampus is a convex structure composed of gray matter tissue inside the para-hippocampal gyrus. It mediates several higher cognitive functions (e.g., learning, long-term memory, spatial navigation, regulation of hypothalamic functions, and emotions).29

The sphenoid sinus could be used as a proper location of an implanted light source. It could provide therapeutic amounts of light to the limbic structures (Fig. 1D). A study made an effort to experimentally examine the light delivery and photon distribution from a transsphenoidal approach, in order to achieve sufficient irradiation of the pars compacta of substantia nigra (SN) in a human cadaver.10 In this study, authors coupled an optical fiber-based light diffuser to a laser diode emitting different wavelengths of 671 or 808 nm, and then the probe was placed in the sphenoidal sinus towards the pars compacta of SN under endoscopic guidance. In compacta of SN, about 0.36% of 808 nm wavelength and 0.03% of 671nm wavelength light emitted by the optical fiber could be reached. When sufficient power was used, these delivered light could provide a sufficient poststimulatory fluence to the SN. In motor planning, movement and reward-seeking, the SN plays an important role.

With transsphenoidal illumination, a reasonable fraction of the light energy could be deposited in the amygdala, hypothalamus, hippocampus, and pituitary gland, before reaching the SN.

ACKNOWLEDGEMENTS

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1I1A1A01052298).

CONFLICT OF INTEREST

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

References
  1. Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng 2012;40:516-33.
    Pubmed KoreaMed CrossRef
  2. Salehpour F, Hamblin MR, DiDuro JO. Rapid reversal of cognitive decline, olfactory dysfunction, and quality of life using multi-modality photobiomodulation therapy: case report. Photobiomodul Photomed Laser Surg 2019;37:159-67.
    Pubmed CrossRef
  3. Chan AS, Lee TL, Yeung MK, Hamblin MR. Photobiomodulation improves the frontal cognitive function of older adults. Int J Geriatr Psychiatry 2019;34:369-77.
    Pubmed KoreaMed CrossRef
  4. Fitzgerald M, Hodgetts S, Van Den Heuvel C, Natoli R, Hart NS, Valter K, et al. Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders. Rev Neurosci 2013;24:205-26.
    Pubmed CrossRef
  5. Grillo SL, Duggett NA, Ennaceur A, Chazot PL. Non-invasive infra-red therapy (1072 nm) reduces β-amyloid protein levels in the brain of an Alzheimer's disease mouse model, TASTPM. J Photochem Photobiol B 2013;123:13-22.
    Pubmed CrossRef
  6. Hamblin MR. Shining light on the head: photobiomodulation for brain disorders. BBA Clin 2016;6:113-24.
    Pubmed KoreaMed CrossRef
  7. Thunshelle C, Hamblin MR. Transcranial low-level laser (Light) therapy for brain injury. Photomed Laser Surg 2016;34:587-98.
    Pubmed KoreaMed CrossRef
  8. Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: case series report. Photomed Laser Surg 2017;35:432-41.
    Pubmed KoreaMed CrossRef
  9. Sun L, Peräkylä J, Kovalainen A, Ogawa KH, Karhunen PJ, Hartikainen KM. Human brain reacts to transcranial extraocular light. PLoS One 2016;11:e0149525.
    Pubmed KoreaMed CrossRef
  10. Pitzschke A, Lovisa B, Seydoux O, Zellweger M, Pfleiderer M, Tardy Y, et al. Red and NIR light dosimetry in the human deep brain. Phys Med Biol 2015;60:2921-37.
    Pubmed CrossRef
  11. Cassano P, Tran AP, Katnani H, Bleier BS, Hamblin MR, Yuan Y, et al. Selective photobiomodulation for emotion regulation: model-based dosimetry study. Neurophotonics 2019;6:015004.
    Pubmed KoreaMed CrossRef
  12. Hanson LR, Frey WH 2nd. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci 2008;9(Suppl 3):S5.
    Pubmed KoreaMed CrossRef
  13. Komorowska M, Cuissot A, Czarnołeski A, Białas W. Erythrocyte response to near-infrared radiation. J Photochem Photobiol B 2002;68:93-100.
    Pubmed CrossRef
  14. Vladimirov YA, Osipov AN, Klebanov GI. Photobiological principles of therapeutic applications of laser radiation. Biochemistry (Mosc) 2004;69:81-90.
    Pubmed CrossRef
  15. Lohr NL, Keszler A, Pratt P, Bienengraber M, Warltier DC, Hogg N. Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J Mol Cell Cardiol 2009;47:256-63.
    Pubmed KoreaMed CrossRef
  16. Asimov MM, Korolevich AN, Konstantinova EÉ. Kinetics of oxygenation of skin tissue exposed to low-intensity laser radiation. J Appl Spectrosc 2007;74:133-9.
  17. Yesman SS, Mamilov SO, Veligotsky DV, Gisbrecht AI. Local changes in arterial oxygen saturation induced by visible and near-infrared light radiation. Lasers Med Sci 2016;31:145-9.
    Pubmed CrossRef
  18. Stadler I, Evans R, Kolb B, Naim JO, Narayan V, Buehner N, et al. In vitro effects of low-level laser irradiation at 660 nm on peripheral blood lymphocytes. Lasers Surg Med 2000;27:255-61.
    Pubmed CrossRef
  19. Chrapko W, Jurasz P, Radomski MW, Archer SL, Newman SC, Baker G, et al. Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients. Neuropsychopharmacology 2006;31:1286-93.
    Pubmed CrossRef
  20. de Lima FM, Villaverde AB, Albertini R, Corrêa JC, Carvalho RL, Munin E, et al. Dual Effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: action on anti- and pro-inflammatory cytokines. Lasers Surg Med 2011;43:410-20.
    Pubmed CrossRef
  21. Oliveira MC Jr, Greiffo FR, Rigonato-Oliveira NC, Custódio RW, Silva VR, Damaceno-Rodrigues NR, et al. Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS. J Photochem Photobiol B 2014;134:57-63.
    Pubmed CrossRef
  22. Karu TI, Pyatibrat LV, Afanasyeva NI. Cellular effects of low power laser therapy can be mediated by nitric oxide. Lasers Surg Med 2005;36:307-14.
    Pubmed CrossRef
  23. Zhang Y, Choksi S, Chen K, Pobezinskaya Y, Linnoila I, Liu ZG. ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res 2013;23:898-914.
    Pubmed KoreaMed CrossRef
  24. Song JW, Li K, Liang ZW, Dai C, Shen XF, Gong YZ, et al. Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats. Sci Rep 2017;7:620.
    Pubmed KoreaMed CrossRef
  25. Byrnes KR, Waynant RW, Ilev IK, Wu X, Barna L, Smith K, et al. Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury. Lasers Surg Med 2005;36:171-85.
    Pubmed CrossRef
  26. Liu TCY, Wu DF, Gu ZQ, Wu M. Applications of intranasal low intensity laser therapy in sports medicine. J Innov Opt Health Sci 2010;03:1-16.
  27. Wiebracht ND, Zimmer LA. Complex anatomy of the sphenoid sinus: a radiographic study and literature review. J Neurol Surg B Skull Base 2014;75:378-82.
    Pubmed KoreaMed CrossRef
  28. Sah P, Faber ES, Lopez De Armentia M, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev 2003;83:803-34.
    Pubmed CrossRef
  29. Anand KS, Dhikav V. Hippocampus in health and disease: an overview. Ann Indian Acad Neurol 2012;15:239-46.
    Pubmed KoreaMed CrossRef
  30. Chao LL. Effects of home photobiomodulation treatments on cognitive and behavioral function, cerebral perfusion, and resting-state functional connectivity in patients with dementia: a pilot trial. Photobiomodul Photomed Laser Surg 2019;37:133-41.
    Pubmed CrossRef
  31. Johnstone DM, Moro C, Stone J, Benabid AL, Mitrofanis J. Turning on lights to stop neurodegeneration: the potential of near infrared light therapy in Alzheimer's and Parkinson's disease. Front Neurosci 2016;9:500.
    KoreaMed CrossRef
  32. Liebert A, Bicknell B, Laakso EL, Heller G, Jalilitabaei P, Tilley S, et al. Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study. BMC Neurol 2021;21:256.
    Pubmed KoreaMed CrossRef
  33. Bogdanova Y, Ho V, Martin P, Ho M, Yee M, Hamblin M, et al. Transcranial LED treatment for cognitive dysfunction and sleep in chronic TBI: randomized controlled pilot trial. Arch Phys Med Rehabil 2017;98:E122-3.
  34. Liu TCY, Cheng L, Su WJ, Zhang YW, Shi Y, Liu AH, et al. Randomized, double-blind, and placebo-controlled clinic report of intranasal low-intensity laser therapy on vascular diseases. Int J Photoenerg 2012;2012:489713.
  35. Caldieraro MA, Sani G, Bui E, Cassano P. Long-term near-infrared photobiomodulation for anxious depression complicated by takotsubo cardiomyopathy. J Clin Psychopharmacol 2018;38:268-70.
    Pubmed CrossRef
  36. Zhao J, Tian Y, Nie J, Xu J, Liu D. Red light and the sleep quality and endurance performance of Chinese female basketball players. J Athl Train 2012;47:673-8.
    Pubmed KoreaMed CrossRef
  37. Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photomed Laser Surg 2011;29:351-8.
    Pubmed KoreaMed CrossRef
  38. Morries LD, Cassano P, Henderson TA. Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy. Neuropsychiatr Dis Treat 2015;11:2159-75.
    Pubmed KoreaMed CrossRef
  39. Liu TCY, Wu DF, Gu ZQ, Wu M. Applications of intranasal low intensity laser therapy in sports medicine. J Innov Opt Health Sci 2010;03:1-16.
  40. Moshkovska T, Mayberry J. It is time to test low level laser therapy in Great Britain. Postgrad Med J 2005;81:436-41.
    Pubmed KoreaMed CrossRef


This Article


Funding Information

Services
Social Network Service

e-submission

Archives