Accessible Requires Authentication Published by De Gruyter December 9, 2019

Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review

Farzad Salehpour, Sevda Gholipour-Khalili, Fereshteh Farajdokht, Farzin Kamari, Tomasz Walski, Michael R. Hamblin, Joseph O. DiDuro and Paolo Cassano


The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted.

  1. Conflict of interest statement: F.S. is on the Scientific Advisory Board and consultant of Niraxx Light Therapeutics Inc., and a consultant of ProNeuroLIGHT LLC. T.W. was supported by the European Union’s Horizon 2020 Research and Innovation Programme, under the Marie Skłodowska-Curie Grant Agreement No 713690, and by the Science Foundation Ireland (SFI) and the European Regional Development Fund (Grant Number 13/RC/2073). P.C.’s salary was supported by the Harvard Psychiatry Department (Dupont-Warren Fellowship and Livingston Award), by the Brain and Behavior Research Foundation (NARSAD Young Investigator Award) and by the Photothera Inc. unrestricted grant. Drug donation from TEVA. Travel reimbursement from Pharmacia-Upjohn. P.C. has received consultation fees from Janssen Research and Development. P.C. has filed a provisional patent related to the use of near-infrared light in psychiatry. PhotoMedex, Inc. supplied four devices for a clinical study. P.C. is/has 1. Received unrestricted funding from Litecure Inc. to conduct a study on transcranial photobiomodulation for the treatment of major depressive disorder; 2. Received unrestricted funding from Cerebral Sciences to conduct a study on transcranial photobiomodulation for the treatment of generalized anxiety disorder; 3. Co-founded, member of the board of directors and consultant of Niraxx Light Therapeutics Inc., a company focused on the development of new modalities of treatment based on near-infrared light. M.R.H. was supported by US NIH Grants R01AI050875 and R21AI121700. M.R.H. is on the following Scientific Advisory Boards: Transdermal Cap Inc., Cleveland, OH, USA; Photothera Inc., Carlsbad, CA, USA; BeWell Global Inc., Wan Chai, Hong Kong; Hologenix Inc., Santa Monica, CA, USA; LumiThera, Inc., Poulsbo, WA, USA; Vielight, Toronto, ON, Canada; Bright Photomedicine, São Paulo, Brazil; Quantum Dynamics LLC, Cambridge, MA, USA; Global Photon Inc, Bee Cave, TX, USA; Medical Coherence, Boston, MA, USA; NeuroThera, Newark, DE, USA; JOOVV Inc., Minneapolis–Saint Paul, MN, USA; AIRx Medical, Inc., Pleasanton, CA, USA; FIR Industries, Inc., Ramsey, NJ, USA; UVLRx Therapeutics, Oldsmar, FL, USA; Ultralux UV Inc., Lansing, MI, USA; Illumiheal&Petthera, Shoreline, WA, USA; MB Laser Therapy, Houston, TX, USA. M.R.H. has been a Consultant for: Lexington int., Boca Raton, FL, USA; USHIO Corp., Japan; Merck KGaA, Darmstadt, Germany; Philips Electronics Nederland B.V.; Johnson & Johnson Inc., Philadelphia, PA; Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany. M.R.H. is a stockholder in Global Photon Inc., Bee Cave, TX, USA and Mitonix, Newark, DE, USA. J.O.D. was a paid business consultant for ProNeuroLIGHT LLC, Kerrville, TX, USA. The other authors have no conflicts of interest to disclose.


Amar, A.P. and Weiss, M.H. (2003). Pituitary anatomy and physiology. Neurosurg. Clin. 14, 11–23. Search in Google Scholar

Anand, K.S. and Dhikav, V. (2012). Hippocampus in health and disease: an overview. Ann. Ind. Acad. Neurol. 15, 239–246. Search in Google Scholar

Arany, P.R., Cho, A., Hunt, T.D., Sidhu, G., Shin, K., Hahm, E., Huang, G.X., Weaver, J., Chen, A.C.-H., Padwa, B.L., et al. (2014). Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci. Transl. Med. 6, 238ra269. Search in Google Scholar

Asimov, M., Korolevich, A., and Konstantinova, E. (2007). Kinetics of oxygenation of skin tissue exposed to low-intensity laser radiation. J. Appl. Spectrosc. 74, 133–139. Search in Google Scholar

Barrett, D.W. and Gonzalez-Lima, F. (2013). Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Neuroscience 230, 13–23. Search in Google Scholar

Bergmann, O., Spalding, K.L., and Frisén, J. (2015). Adult neurogenesis in humans. Cold Spring Harb. Perspect. Biol. 7, a018994. Search in Google Scholar

Berman, M.H., Halper, J.P., Nichols, T.W., Jarrett, H., Lundy, A., and Huang, J.H. (2017). Photobiomodulation with near infrared light helmet in a pilot, placebo controlled clinical trial in dementia patients testing memory and cognition. J. Neurol. Neurosci. 8, 171–178. Search in Google Scholar

Bogdanova, Y., Ho, V., Martin, P., Ho, M., Yee, M., Hamblin, M., and Naeser, M. (2017). Transcranial LED treatment for cognitive dysfunction and sleep in chronic TBI: randomized controlled pilot trial. Arch. Phys. Med. Rehabil. 98, e122–e123. Search in Google Scholar

Bomboi, G., Castello, L., Cosentino, F., Giubilei, F., Orzi, F., and Volpe, M. (2010). Alzheimer’s disease and endothelial dysfunction. Neurol. Sci. 31, 1–8. Search in Google Scholar

Brill, A.G., Shenkman, B., Brill, G.E., Tamarin, I., Dardik, R., Kirichuk, V.F., Savion, N., and Varon, D. (2000). Blood irradiation by He-Ne laser induces a decrease in platelet responses to physiological agonists and an increase in platelet cyclic GMP. Platelets 11, 87–93. Search in Google Scholar

Budu, V., Mogoanta, C.A., Fanuta, B., and Bulescu, I. (2013). The anatomical relations of the sphenoid sinus and their implications in sphenoid endoscopic surgery. Rom. J. Morphol. Embryol. 54, 13–16. Search in Google Scholar

Burchman, M.A. (2011). Using photobiomodulation on a severe Parkinson’s patient to enable extractions, root canal treatment, and partial denture fabrication. J. Laser Dent. 19, 297–300. Search in Google Scholar

Byrnes, K.R., Waynant, R.W., Ilev, I.K., Wu, X., Barna, L., Smith, K., Heckert, R., Gerst, H., and Anders, J.J. (2005). Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury. Lasers Surg. Med. 36, 171–185. Search in Google Scholar

Caldieraro, M.A. and Cassano, P. (2019). Transcranial and systemic photobiomodulation for major depressive disorder: a systematic review of efficacy, tolerability and biological mechanisms. J. Affect. Disord. 243, 262–273. Search in Google Scholar

Caldieraro, M.A., Sani, G., Bui, E., and Cassano, P. (2018). Long-term near-infrared photobiomodulation for anxious depression complicated by Takotsubo cardiomyopathy. J. Clin. Psychopharmacol. 38, 268–270. Search in Google Scholar

Cassano, P., Tran, A.P., Katnani, H., Bleier, B.S., Hamblin, M.R., Yuan, Y., and Fang, Q. (2019). Selective photobiomodulation for emotion regulation: model-based dosimetry study. Neurophotonics 6, 015004. Search in Google Scholar

Chan, A.S., Lee, T.L., Yeung, M.K., and Hamblin, M.R. (2019). Photobiomodulation improves the frontal cognitive function of older adults. Int. J. Geriatr. Psychiatry 34, 369–377. Search in Google Scholar

Chang, J., Wang, R., Li, C., Wang, Y., and Chu, X.-P. (2018). Transcranial low-level laser therapy for depression and Alzheimer’s disease. Neuropsychiatry 8, 477–483. Search in Google Scholar

Chao, L.L. (2019). 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. 37, 133–141. Search in Google Scholar

Chen, Y. and Cheng, H. (2004). Clinical observation of the integrated therapy of intranasal low intensity He-Ne laser therapy and herb therapy on insomnia. J. Tradit. Chin. Med. 24, 38. Search in Google Scholar

Cheon, S.Y., Kim, E.J., Kim, J.M., Kam, E.H., Ko, B.W., and Koo, B.-N. (2017). Regulation of microglia and macrophage polarization via apoptosis signal-regulating kinase 1 silencing after ischemic/hypoxic injury. Front. Mol. Neurosci. 10, 261. Search in Google Scholar

Chludzińska, L., Ananicz, E., Jarosawska, A., and Komorowska, M. (2005). Near-infrared radiation protects the red cell membrane against oxidation. Blood Cells Mol. Dis. 35, 74–79. Search in Google Scholar

Choi, R. and Goldstein, B.J. (2018). Olfactory epithelium: cells, clinical disorders, and insights from an adult stem cell niche. Laryngoscope Investig. Otolaryngol. 3, 35–42. Search in Google Scholar

Chrapko, W., Jurasz, P., Radomski, M.W., Archer, S.L., Newman, S.C., Baker, G., Lara, N., and Le Mellédo, J.-M. (2006). Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients. Neuropsychopharmacology 31, 1286. Search in Google Scholar

Chung, H., Dai, T., Sharma, S.K., Huang, Y.-Y., Carroll, J.D., and Hamblin, M.R. (2012). The nuts and bolts of low-level laser (light) therapy. Ann. Biomed. Eng. 40, 516–533. Search in Google Scholar

Cicerone, K.D. and Tanenbaum, L.N. (1997). Disturbance of social cognition after traumatic orbitofrontal brain injury. Arch. Clin. Neuropsychol. 12, 173–188. Search in Google Scholar

Clark, D.L., Boutros, N.N., and Mendez, M.F. (2018). Frontal lobe. In: The Brain and Behavior: An Introduction to Behavioral Neuroanatomy. D.L. Clark, M.F. Mendez, and N.N. Boutros, eds. (Cambridge: Cambridge University Press). pp. 73–102. Search in Google Scholar

Cragg, S.J., Baufreton, J., Xue, Y., Bolam, J.P., and Bevan, M.D. (2004). Synaptic release of dopamine in the subthalamic nucleus. Eur. J. Neurosci. 20, 1788–1802. Search in Google Scholar

de Freitas, L.F. and Hamblin, M.R. (2016). Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J. Sel. Top. Quantum Electron. 22, 348–364. Search in Google Scholar

de Lima, F.M., Villaverde, A., Albertini, R., Corrêa, J., Carvalho, R., Munin, E., Araújo, T., Silva, J., and Aimbire, F. (2011). 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. 43, 410–420. Search in Google Scholar

Delong, M.R., Crutcher, M.D., and Georgopoulos, A.P. (1983). Relations between movement and single cell discharge in the substantia nigra of the behaving monkey. J. Neurosci. 3, 1599–1606. Search in Google Scholar

DiMauro, T.M., Attawia, M., Lilienfeld, S., and Holy, C. (2008). Intranasal red light probe for treating Alzheimer’s disease. Google Patents. Search in Google Scholar

DiMauro, T.M., Attawia, M., Lilienfeld, S., and Holy, C. (2014). Intranasal red light probe for treating Alzheimer’s disease. Google Patents. Search in Google Scholar

DiMauro, T.M., Wildenhaus, K., Pracyk, J., and Luedtke, M. (2018). Intranasal insert for OFC neuroprotection. Google Patents. Search in Google Scholar

Dou, Z., Xiquan, H., and Zhu, H. (2003). The effects of two kinds of laser irradiation on patients with brain lesion. Chin. J. Phys. Med. Rehabil. 2, 38–43. Search in Google Scholar

Drohomirecka, A., Iwaszko, A., Walski, T., Pliszczak-Król, A., Wąż, G., Graczyk, S., Gałecka, K., Czerski, A., Bujok, J., and Komorowska, M. (2018). Low-level light therapy reduces platelet destruction during extracorporeal circulation. Sci. Rep. 8, 16963. Search in Google Scholar

Ehrlich, I., Humeau, Y., Grenier, F., Ciocchi, S., Herry, C., and Lüthi, A. (2009). Amygdala inhibitory circuits and the control of fear memory. Neuron 62, 757–771. Search in Google Scholar

El Massri, N., Lemgruber, A.P., Rowe, I.J., Moro, C., Torres, N., Reinhart, F., Chabrol, C., Benabid, A.-L., and Mitrofanis, J. (2017). Photobiomodulation-induced changes in a monkey model of Parkinson’s disease: changes in tyrosine hydroxylase cells and GDNF expression in the striatum. Exp. Brain Res. 235, 1861–1874. Search in Google Scholar

Elwood, P.C., Pickering, J., and Gallacher, J.E. (2001). Cognitive function and blood rheology: results from the Caerphilly cohort of older men. Age Ageing 30, 135–139. Search in Google Scholar

Erdem, G., Erdem, T., Miman, M.C., and Ozturan, O. (2004). A radiological anatomic study of the cribriform plate compared with constant structures. Rhinology 42, 225–229. Search in Google Scholar

Fitzgerald, M., Hodgetts, S., Van Den Heuvel, C., Natoli, R., Hart, N.S., Valter, K., Harvey, A.R., Vink, R., Provis, J., and Dunlop, S.A. (2013). Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders. Rev. Neurosci. 24, 205–226. Search in Google Scholar

Freeman, J.L. (2003). The anatomy and embryology of the hypothalamus in relation to hypothalamic hamartomas. Epileptic Disord. 5, 177–186. Search in Google Scholar

Frey, W. (1991). Neurologic agents for nasal administration to the brain. World Intellect. Prop. Organ. 5, 89. Search in Google Scholar

Fukuzaki, Y., Sugawara, H., Yamanoha, B., and Kogure, S. (2013). 532 nm low-power laser irradiation recovers γ-secretase inhibitor-mediated cell growth suppression and promotes cell proliferation via Akt signaling. PLoS One 8, e70737. Search in Google Scholar

Fukuzaki, Y., Shin, H., Kawai, H.D., Yamanoha, B., and Kogure, S. (2015). 532 nm low-power laser irradiation facilitates the migration of GABAergic neural stem/progenitor cells in mouse neocortex. PLoS One 10, e0123833. Search in Google Scholar

Ganeshan, V., Skladnev, N.V., Kim, J.Y., Mitrofanis, J., Stone, J., and Johnstone, D.M. (2019). Pre-conditioning with remote photobiomodulation modulates the brain transcriptome and protects against MPTP insult in mice. Neuroscience 400, 85–97. Search in Google Scholar

Gao, Z.-S., Zhang, L., and Qin, C.-l. (2004). The relationship between hemorheological changes and the anxiety and depression symptoms in schizophrenia. Chin. J. Hemorheol. 1. Search in Google Scholar

Gao, X., Zhi, P., and Wu, X. (2008). Low-energy semiconductor laser intranasal irradiation of the blood improves blood coagulation status in normal pregnancy at term. Nan Fang Yi Ke Da Xue Xue Bao 28, 1400–1401. Search in Google Scholar

Gisbrecht, A., Mamilov, S., Esman, S., and Asimov, M. (2017). Estimation of the quantum efficiency of the photodissociation of HbO2 and HbCO. 19th International Conference and School on Quantum Electronics: Laser Physics and Applications. International Society for Optics and Photonics, p. 1022619. Search in Google Scholar

Gloor, P. (1978). Inputs and Outputs of the Amygdala: What the Amygdala is Trying to Tell the Rest of the Brain. Limbic Mechanisms (Boston, MA, USA: Springer), pp. 189–209. Search in Google Scholar

Greicius, M.D., Srivastava, G., Reiss, A.L., and Menon, V. (2004). Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc. Natl Acad Sci. U.S.A. 101, 4637–4642. Search in Google Scholar

Grillo, S.L., Duggett, N.A., Ennaceur, A., and Chazot, P.L. (2013). 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 Biol. 123, 13–22. Search in Google Scholar

Hajos, M. and Greenfield, S. (1994). Synaptic connections between pars compacta and pars reticulata neurones: electrophysiological evidence for functional modules within the substantia nigra. Brain Res. 660, 216–224. Search in Google Scholar

Hamblin, M.R. (2016). Shining light on the head: photobiomodulation for brain disorders. BBA Clin. 6, 113–124. Search in Google Scholar

Henderson, T.A. and Morries, L.D. (2015). Near-infrared photonic energy penetration: can infrared phototherapy effectively reach the human brain? Neuropsychiatr. Dis. Treat. 11, 2191. Search in Google Scholar

Hennessy, M. and Hamblin, M.R. (2016). Photobiomodulation and the brain: a new paradigm. J. Opt. 19, 013003. Search in Google Scholar

Herisson, F., Frodermann, V., Courties, G., Rohde, D., Sun, Y., Vandoorne, K., Wojtkiewicz, G.R., Masson, G.S., Vinegoni, C., Kim, J., et al. (2018). Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat. Neurosci. 21, 1209–1217. Search in Google Scholar

Hiser, J. and Koenigs, M. (2018). The multifaceted role of the ventromedial prefrontal cortex in emotion, decision making, social cognition, and psychopathology. Biol. Psychiatr. 83, 638–647. Search in Google Scholar

Hroudová, J., Fišar, Z., Kitzlerová, E., Zvěřová, M., and Raboch, J. (2013). Mitochondrial respiration in blood platelets of depressive patients. Mitochondrion 13, 795–800. Search in Google Scholar

Iaccarino, H.F., Singer, A.C., Martorell, A.J., Rudenko, A., Gao, F., Gillingham, T.Z., Mathys, H., Seo, J., Kritskiy, O., and Abdurrob, F. (2016). Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540, 230. Search in Google Scholar

Ilango, A., Kesner, A.J., Keller, K.L., Stuber, G.D., Bonci, A., and Ikemoto, S. (2014). Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion. J. Neurosci. 34, 817–822. Search in Google Scholar

Insausti, R. and Amaral, D.G. (2012). Chapter 24 – hippocampal formation. In: The Human Nervous System (Third Edition). J.K. Mai and G. Paxinos, eds. (San Diego: Academic Press). pp. 896–942. Search in Google Scholar

Itoh, T., Murakami, H., Orihashi, K., Sueda, T., and Matsuura, Y. (1996). The protective effect of low power He-Ne laser against erythrocytic damage caused by artificial heart-lung machines. Hiroshima J. Med. Sci. 45, 15–22. Search in Google Scholar

Jagdeo, J.R., Adams, L.E., Brody, N.I., and Siegel, D.M. (2012). Transcranial red and near infrared light transmission in a cadaveric model. PLoS One 7, e47460. Search in Google Scholar

Jianbo, X., Qiuyun, C., and Jianxin, X. (1999). Effects of laser irradiation therapy through nasal cavity on viscosity at lower shear rates and hematocrit in patients with acute ischemic cerebrovascular disease (AICVD). J. Binzhou Med. Coll. 6, 006. Search in Google Scholar

Jiang, Y., Li, Y., and Liu, X. (2015). Intranasal delivery: circumventing the iron curtain to treat neurological disorders. Expert. Opin. Drug Deliv. 12, 1717–1725. Search in Google Scholar

Jiao, J.-L., Liu, T.C.-Y., Liu, J., Cui, L.-P., and Liu, S.-H. (2006). Advances in endonasal low intensity laser irradiation therapy. 2004 Shanghai International Conference on Laser Medicine and Surgery. International Society for Optics and Photonics, p. 59671C. Search in Google Scholar

Jin, L., Shi, B., and Zhou, C. (2000). The effecton serum amyloid bprotein of patients with mild cognitive impairment after semiconductor laser therapy. Acta Acad. Med. Qingdao Univ. 36, 175–176. Search in Google Scholar

Jing, W.Y.Z. (1999). Vascular low level laser irradiation therapy in treatment of brain injury. Acta Laser Biol. Sin. 8. Search in Google Scholar

Karu, T. (1988). Molecular mechanism of the therapeutic effect of low-intensity laser radiation. Lasers Life Sci. 2, 53–74. Search in Google Scholar

Karu, T.I. (2010). Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life 62, 607–610. Search in Google Scholar

Karu, T.I., Pyatibrat, L.V., and Afanasyeva, N.I. (2005). Cellular effects of low power laser therapy can be mediated by nitric oxide. Lasers Surg. Med. 36, 307–314. Search in Google Scholar

Koh, E., Frazzini, V.I., and Kagetsu, N.J. (2000). Epistaxis: vascular anatomy, origins, and endovascular treatment. Am. J. Roentgenol. Radium 174, 845–851. Search in Google Scholar

Komorowska, M., Cuissot, A., Czarnoleski, A., and Bialas, W. (2001). Erythrocyte response to near infrared radiation. Cell. Mol. Biol. Lett. 6, 212. Search in Google Scholar

Komorowska, M., Cuissot, A., Czarnołȩski, A., and Białas, W. (2002). Erythrocyte response to near-infrared radiation. J. Photochem. Photobiol. B Biol. 68, 93–100. Search in Google Scholar

Kujawa, J., Zavodnik, L., Zavodnik, I., Buko, V., Lapshyna, A., and Bryszewska, M. (2004). Effect of low-intensity (3.75–25 J/cm2) near-infrared (810 nm) laser radiation on red blood cell ATPase activities and membrane structure. J. Clin. Laser Med. Surg. 22, 111–117. Search in Google Scholar

Lavoie, B., Smith, Y., and Parent, A. (1989). Dopaminergic innervation of the basal ganglia in the squirrel monkey as revealed by tyrosine hydroxylase immunohistochemistry. J. Comp. Neurol. 289, 36–52. Search in Google Scholar

LeDoux, J. (2007). The amygdala. Curr. Biol. 17, R868–R874. Search in Google Scholar

Levin, H., High, W., and Eisenberg, H. (1985). Impairment of olfactory recognition after closed head injury. Brain 108, 579–591. Search in Google Scholar

Li, Q., Guo, K., Kang, J., and Jiang, B. (1998a). Clinic analysis of endonasal low energy He-Ne laser treatment of 39 cases of intractable headache. Acta Acad. Med. Qingdao Univ. 1, 53. Search in Google Scholar

Li, Q., Guo, K., Kang, J., Jiang, B., and Wang, Y. (1998b). β endorphin research for endonasal low energy He-Ne laser treatment of ache in head or face. Chin. J. Neurol. 31, 91. Search in Google Scholar

Li, Q., Kang, J., Song, Y., Shen, L., Liu, Z., and Tan, J. (1999a). Electron microscope observation of erythrocytes of cerebral thrombosis treated by endonasal low energy He-Ne laser. Shandong Med. Pharm. 39, 3–4. Search in Google Scholar

Li, Q., Song, L., Guo, K., Yu, Y., Ma, S., and Shen, L. (1999b). The effect of endonasal low energy He-Ne laser treatment of Parkinson’s disease on CCK-8 content in blood. Chin. J. Neurol. 32, 364. Search in Google Scholar

Li, Q.-M., Guo, K., and Tang, J.-Q. (1999c). Effects on plasma CCK-8 content of low power laser nasal cavity directional irradiation in treatment on Parkinson. Chin. J. Neurol. 32, 364. Search in Google Scholar

Liao, Z. (2000). Nursing patients of schizophrenia treated by intranasal low energy He-Ne laser therapy. J. Jiangxi Uni. Tradit. Chin. Med. 12, 140. Search in Google Scholar

Lim, L. (2014). Intranasal Photobiomodulation Improves Cognitive and Memory Performance of Alzheimer’s Disease Patients in Case Studies (NAALT/WALT, Arlington, Virginia, USA). Search in Google Scholar

Litscher, D. and Litscher, G. (2013). Laser therapy and stroke: quantification of methodological requirements in consideration of yellow laser. Int. J. Photoenergy 575798, 1–4. Search in Google Scholar

Liu, T.C.-Y., Jiaob, J.-L., Lianga, J., and Liu, S.-H. (2007). Mechanism of Itranasal Low Intensity Laser Irradiation Therapy. World Symposium on TCM Acupuncture and Moxibustion, Tarragona, Spain. Search in Google Scholar

Liu, T.C.-Y., Wu, D.-F., Gu, Z.-Q., and Wu, M. (2010). Applications of intranasal low intensity laser therapy in sports medicine. J. Innov. Opt. Health Sci. 3, 1–16. Search in Google Scholar

Liu, T.C.-Y., Cheng, L., Su, W.-J., Zhang, Y.-W., Shi, Y., Liu, A.-H., Zhang, L.-L., and Qian, Z.-Y. (2012). Randomized, double-blind, and placebo-controlled clinic report of intranasal low-intensity laser therapy on vascular diseases. Int. J. Photoenergy 489713, 1–5. Search in Google Scholar

Lohr, N.L., Keszler, A., Pratt, P., Bienengraber, M., Warltier, D.C., and Hogg, N. (2009). Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J. Mol. Cell. Cardiol. 47, 256–263. Search in Google Scholar

MacArthur, F.J. and McGarry, G.W. (2017). The arterial supply of the nasal cavity. Eur. Arch. Otorhinolaryngol. 274, 809–815. Search in Google Scholar

Maksimovich, I.V. (2004). Transluminal laser angioplasty in treatment of ischemic lesions of a brain. MD Dissertation (Russian University of Friendship of the People, Moscow). Search in Google Scholar

Marianecci, C., Rinaldi, F., Hanieh, P.N., Di Marzio, L., Paolino, D., and Carafa, M. (2017). Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting. Drug Des. Devel. Ther. 11, 325. Search in Google Scholar

Masurkar, A.V. and Chen, W.R. (2009). Olfactory bulb physiology. In: Encyclopedia of Neuroscience. L.R. Squire, ed. (Oxford: Academic Press). pp. 77–86. Search in Google Scholar

Mi, X., Chen, J., Cen, Y., Liang, Z., and Zhou, L. (2004). A comparative study of 632.8 and 532 nm laser irradiation on some rheological factors in human blood in vitro. J. Photochem. Photobiol. B, Biol. 74, 7–12. Search in Google Scholar

Michalikova, S., Ennaceur, A., van Rensburg, R., and Chazot, P.L. (2008). Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light. Neurobiol. Learn. Mem. 89, 480–488. Search in Google Scholar

Moore, K., Dalley, A., and Agur, A. (1999). Clinically Oriented Anatomy (Philadelphia: Lippincott, Williams & Wilkins). Search in Google Scholar

Morries, L.D., Cassano, P., and Henderson, T.A. (2015). Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy. Neuropsychiatr. Dis. Treat. 11, 2159. Search in Google Scholar

Moshkovska, T. and Mayberry, J. (2005). It is time to test low level laser therapy in Great Britain. Postgrad. Med. J. 81, 436–441. Search in Google Scholar

Myers-Schulz, B. and Koenigs, M. (2012). Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders. Mol. Psychiatr. 17, 132–141. Search in Google Scholar

Naeser, M.A., Saltmarche, A., Krengel, M.H., Hamblin, M.R., and Knight, J.A. (2011). Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photobiomodul. Photomed. Laser Surg. 29, 351–358. Search in Google Scholar

Naeser, M.A., Zafonte, R., Krengel, M.H., Martin, P.I., Frazier, J., Hamblin, M.R., Knight, J.A., Meehan III, W.P., and Baker, E.H. (2014). Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. J. Neurotrauma 31, 1008–1017. Search in Google Scholar

Natzle, W.C. and Moore, C.B. (1985). Recombination of hydrogen ion (H+) and hydroxide in pure liquid water. J. Phys. Chem. 89, 2605–2612. Search in Google Scholar

Natzle, W.C., Moore, C.B., Goodall, D., Frisch, W., and Holzwarth, J. (1981). Dissociative ionization of water induced by single-photon vibrational excitation. J. Phys. Chem. 85, 2882–2884. Search in Google Scholar

Netter, F.H. (2017). Atlas of Human Anatomy E-Book (Elsevier Health Sciences, Philadelphia, PA, USA), pp. 61–64. Search in Google Scholar

Oliveira Jr, M.C., Greiffo, F.R., Rigonato-Oliveira, N.C., Custódio, R.W.A., Silva, V.R., Damaceno-Rodrigues, N.R., Almeida, F.M., Albertini, R., Lopes-Martins, R.Á.B., and de Oliveira, L.V.F. (2014). Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS. J. Photochem. Photobiol. B, Biol. 134, 57–63. Search in Google Scholar

Parent, A.D. and Perkins, E. (2018). Chapter 30 – the hypothalamus. In: Fundamental Neuroscience for Basic and Clinical Applications (Fifth Edition). D.E. Haines and G.A. Mihailoff, eds. (Elsevier). pp. 442–456. Search in Google Scholar

Pfleiderer, M., Tardy, Y.S., and Lovisa, B. (2017). Transnasal delivery of low level light via the sphenoidal sinus to irradiate the substantia nigra. Google Patents. Search in Google Scholar

Pitzschke, A., Lovisa, B., Seydoux, O., Zellweger, M., Pfleiderer, M., Tardy, Y., and Wagnières, G. (2015). Red and NIR light dosimetry in the human deep brain. Phys. Med. Biol. 60, 2921. Search in Google Scholar

Rajagopal, M. and Paul, J. (2005). Applied anatomy and physiology of the airway and breathing. Ind. J. Anaesth. 49, 251–256. Search in Google Scholar

Ritchie, K. and Touchon, J. (2000). Mild cognitive impairment: conceptual basis and current nosological status. Lancet 355, 225–228. Search in Google Scholar

Ritter, F.N. (1970). The vasculature of the nose. Ann. Otol. Rhinol. Laryngol. 79, 468–474. Search in Google Scholar

Rola, P., Doroszko, A., Szahidewicz-Krupska, E., Rola, P., Dobrowolski, P., Skomro, R., Szymczyszyn, A., Mazur, G., and Derkacz, A. (2017). Low-level laser irradiation exerts antiaggregative effect on human platelets independently on the nitric oxide metabolism and release of platelet activation markers. Oxid. Med. Cell. Longev. 2017, Search in Google Scholar

Rolls, E.T. and Grabenhorst, F. (2008). The orbitofrontal cortex and beyond: from affect to decision-making. Prog. Neurobiol. 86, 216–244. Search in Google Scholar

Roy, M., Shohamy, D., and Wager, T.D. (2012). Ventromedial prefrontal-subcortical systems and the generation of affective meaning. Trends Cogn. Sci. 16, 147–156. Search in Google Scholar

Rudebeck, P.H., Mitz, A.R., Chacko, R.V., and Murray, E.A. (2013). Effects of amygdala lesions on reward-value coding in orbital and medial prefrontal cortex. Neuron 80, 1519–1531. Search in Google Scholar

Sah, P., Faber, E.L., Lopez de Armentia, M., and Power, J. (2003). The amygdaloid complex: anatomy and physiology. Physiol. Rev. 83, 803–834. Search in Google Scholar

Salehpour, F., De Taboada, L., Cassano, P., Kamari, F., Mahmoudi, J., Ahmadi-Kandjani, S., Rasta, S.H., and Sadigh-Eteghad, S. (2018a). A protocol for transcranial photobiomodulation therapy in mice. J. Vis. Exp. e59076. Search in Google Scholar

Salehpour, F., Mahmoudi, J., Kamari, F., Sadigh-Eteghad, S., Rasta, S.H., and Hamblin, M.R. (2018b). Brain photobiomodulation therapy: a narrative review. Mol. Neurobiol. 55, 6601–6636. Search in Google Scholar

Salehpour, F., Hamblin, M.R., and DiDuro, J.O. (2019). Rapid reversal of cognitive decline, olfactory dysfunction, and quality of life using multi-modality photobiomodulation therapy: case report. Photobiomodul. Photomed. Laser Surg. 37, 159–167. Search in Google Scholar

Saltmarche, A.E., Naeser, M.A., Ho, K.F., Hamblin, M.R., and Lim, L. (2017). Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: case series report. Photobiomodul. Photomed. Laser Surg. 35, 432–441. Search in Google Scholar

Sommer, A.P. and Trelles, M.A. (2014). Light pumping energy into blood mitochondria: a new trend against depression? Photobiomodul. Photomed. Laser Surg. 32, 59–60. Search in Google Scholar

Song, J.W., Li, K., Liang, Z.W., Dai, C., Shen, X.F., Gong, Y.Z., Wang, S., Hu, X.Y., and Wang, Z. (2017). Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats. Sci. Rep. 7, 620. Search in Google Scholar

Song-Lin, X. (1997). Laser medicine. Chin. Med. J. 76, 939–940. Search in Google Scholar

Stadler, I., Evans, R., Kolb, B., Naim, J.O., Narayan, V., Buehner, N., and Lanzafame, R.J. (2000). In vitro effects of low-level laser irradiation at 660 nm on peripheral blood lymphocytes. Lasers Surg. Med. 27, 255–261. Search in Google Scholar

Stern, M., Broja, M., Sansone, R., Gröne, M., Skene, S.S., Liebmann, J., Suschek, C.V., Born, M., Kelm, M., and Heiss, C. (2018). Blue light exposure decreases systolic blood pressure, arterial stiffness, and improves endothelial function in humans. Eur. J. Prev. Cardiol. 25, 1875–1883. Search in Google Scholar

Sun, L., Peräkylä, J., Kovalainen, A., Ogawa, K.H., Karhunen, P.J., and Hartikainen, K.M. (2016). Human brain reacts to transcranial extraocular light. PLoS One 11, e0149525. Search in Google Scholar

Szymborska-Małek, K., Komorowska, M., and Gąsior-Głogowska, M. (2018). Effects of near infrared radiation on DNA. DLS and ATR-FTIR study. Spectrochim. Acta A Mol. Biomol. Spectrosc. 188, 258–267. Search in Google Scholar

Te Alexis, E. (2006). The next generation in laser treatments and the role of the green light high-performance system laser. Rev. Urol. 8, S24. Search in Google Scholar

Thunshelle, C. and Hamblin, M.R. (2016). Transcranial low-level laser (light) therapy for brain injury. Photobiomodul. Photomed. Laser Surg. 34, 587–598. Search in Google Scholar

Va, M. (2015). The use of intravenous laser blood irradiation (ILBI) at 630-640 nm to prevent vascular diseases and to increase life expectancy. Laser Ther. 24, 15–26. Search in Google Scholar

Vladimirov, Y.A., Osipov, A., and Klebanov, G. (2004). Photobiological principles of therapeutic applications of laser radiation. Biochemistry (Mosc) 69, 81–90. Search in Google Scholar

Walski, T., Chludzińska, L., Komorowska, M., and Witkiewicz, W. (2014). Individual osmotic fragility distribution: a new parameter for determination of the osmotic properties of human red blood cells. Biomed. Res. Int. 2014, 162102. Search in Google Scholar

Walski, T., Dyrda, A., Dzik, M., Chludzińska, L., Tomków, T., Mehl, J., Detyna, J., Gałecka, K., Witkiewicz, W., and Komorowska, M. (2015). Near infrared light induces post-translational modifications of human red blood cell proteins. Photochem. Photobiol. Sci. 14, 2035–2045. Search in Google Scholar

Walski, T., Drohomirecka, A., Bujok, J., Czerski, A., Wąż, G., Trochanowska, N., Gorczykowski, M., Cichoń, R., and Komorowska, M. (2018). Low-level light therapy protects red blood cells against oxidative stress and haemolysis during extracorporeal circulation. Front. Physiol. 9, 647. Search in Google Scholar

Wang, H., Deng, J., Tu, W., Zhang, L., Chen, H., Wu, X., Li, Y., and Sha, H. (2016). The hematologic effects of low intensity 650 nm laser irradiation on hypercholesterolemia rabbits. Am. J. Transl. Res. 8, 2293. Search in Google Scholar

Wiebracht, N.D. and Zimmer, L.A. (2014). Complex anatomy of the sphenoid sinus: a radiographic study and literature review. J. Neurol. Surg. B Skull Base 75, 378–382. Search in Google Scholar

Wilson, R.S., Yu, L., and Bennett, D.A. (2010). Odor identification and mortality in old age. Chem. Senses 36, 63–67. Search in Google Scholar

Xiao, X.-C., Jia, S.-W., and Zheng, X.-Y. (2001). Study on SPECT for intravascular laser irradiation treatment on cerebral infarction. Chin. J. Phys. Ther. 24, 133–135. Search in Google Scholar

Xiao, X., Guo, Y., Chu, X., Jia, S., Zheng, X., and Zhou, C. (2005). Effects of low power laser irradiation in nasal cavity on cerebral blood flow perfusion of patients with brain infarction. Chin. J. Phys. Med. 27, 418–420. Search in Google Scholar

Xie, T., Vigil, J., MacCracken, E., Gasparaitis, A., Young, J., Kang, W., Bernard, J., Warnke, P., and Kang, U.J. (2015). Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology 84, 415–420. Search in Google Scholar

Xu, C., Wang, L., Liu, J., Tan, Y., and Li, Q. (2001). Endonasal low energy He-Ne laser treatment of insomnia. Qian. Wei. J. Med. Pharm. 18, 337–338. Search in Google Scholar

Xu, C., Wang, L., and Lu, C. (2002a). Endonasal low energy He-Ne laser treatment of poststroke depression. Prac. J. Med. Pharm. 19, 893. Search in Google Scholar

Xu, C., Wang, L., Shang, X., and Li, Q. (2002b). Endonasal low energy He-Ne laser treatment of Alzheimer’s disease. Prac. J. Med. Pharm. 19, 647–648. Search in Google Scholar

Xu, C., Wu, Z., Wang, L., Shang, X., and Li, Q. (2002c). The effects of endonasal low energy He–Ne laser treatment of insomnia on sleep EEG. Prac. J. Med. Pharm. 19, 407–408. Search in Google Scholar

Xu, C., Lu, C., Wang, L., and Li, Q. (2003). The effects of endonasal low energy He-Ne laser therapy on antioxydation of Parkinson’s disease. Prac. J. Med. Pharm. 20, 816–817. Search in Google Scholar

Xuan, W., Vatansever, F., Huang, L., and Hamblin, M.R. (2014). Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice. J. Biomed. Opt. 19, 108003. Search in Google Scholar

Yang, J., Zhang, Q., Li, P., Dong, T., and Wu, M.X. (2016). Low-level light treatment ameliorates immune thrombocytopenia. Sci. Rep. 6, 38238. Search in Google Scholar

Yesman, S., Mamilov, S., Veligotsky, D., and Gisbrecht, A. (2016). Local changes in arterial oxygen saturation induced by visible and near-infrared light radiation. Lasers Med. Sci. 31, 145–149. Search in Google Scholar

Zein, R., Selting, W., and Hamblin, M.R. (2018). Review of light parameters and photobiomodulation efficacy: dive into complexity. J. Biomed. Opt. 23, 120901. Search in Google Scholar

Zhang, Y., Choksi, S., Chen, K., Pobezinskaya, Y., Linnoila, I., and Liu, Z.-G. (2013). ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res. 23, 898. Search in Google Scholar

Zhang, Q., Dong, T., Li, P., and Wu, M.X. (2016). Noninvasive low-level laser therapy for thrombocytopenia. Sci. Transl. Med. 8, 349ra101. Search in Google Scholar

Zhang, Q., Lu, M., and Wu, M.X. (2018). Prolonging shelf-life of platelets by low-level laser. Mechanisms of Photobiomodulation Therapy XIII. Proc SPIE, International Society for Optics and Photonics. 10477, 104770D. Search in Google Scholar

Zhao, G., Guo, K., and Dan, J. (2003). Case analysis of Parkinson’s disease treated by endonasal low energy He-Ne laser. Acta. Acad. Med. Q+ingdao Univ. 39, 398. Search in Google Scholar

Zhao, J., Tian, Y., Nie, J., Xu, J., and Liu, D. (2012). Red light and the sleep quality and endurance performance of Chinese female basketball players. J. Athl. Train. 47, 673–678. Search in Google Scholar

Zheng, W., Li, D., Zeng, Y., Luo, Y., and Qu, J.Y. (2011). Two-photon excited hemoglobin fluorescence. Biomed. Opt. Exp. 2, 71–79. Search in Google Scholar

Zomorrodi, R., Saltmarche, A.E., Loheswaran, G., Ho, K.F., and Lim, L. (2017). Complementary EEG evidence for a significantly improved Alzheimer’s disease case after photobiomodulation treatment. Alzheimer’s Association International Conference. p. P621. Search in Google Scholar

Zomorrodi, R., Genane, L., Abhiram, P., and Lew, L. (2019). Pulsed near infrared transcranial and intranasal photobiomodulation significantly modulates neural oscillations: a pilot exploratory study. Sci. Rep. 9, 6309. Search in Google Scholar

Zubia, J. and Arrue, J. (2001). Plastic optical fibers: an introduction to their technological processes and applications. Opt. Fiber Technol. 7, 101–140. Search in Google Scholar

Received: 2019-06-29
Accepted: 2019-09-22
Published Online: 2019-12-09
Published in Print: 2020-04-28

©2020 Walter de Gruyter GmbH, Berlin/Boston