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

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          Abstract

          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.

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          Gamma frequency entrainment attenuates amyloid load and modifies microglia.

          Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1-40 and Aβ 1-42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ1-40 and Aβ1-42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
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            Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI.

            Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have also shown decreased metabolism early in the course of Alzheimer's disease (AD). We reasoned that default-mode network activity might therefore be abnormal in AD. To test this hypothesis, we used independent component analysis to isolate the network in a group of 13 subjects with mild AD and in a group of 13 age-matched elderly controls as they performed a simple sensory-motor processing task. Three important findings are reported. Prominent coactivation of the hippocampus, detected in all groups, suggests that the default-mode network is closely involved with episodic memory processing. The AD group showed decreased resting-state activity in the posterior cingulate and hippocampus, suggesting that disrupted connectivity between these two regions accounts for the posterior cingulate hypometabolism commonly detected in positron emission tomography studies of early AD. Finally, a goodness-of-fit analysis applied at the individual subject level suggests that activity in the default-mode network may ultimately prove a sensitive and specific biomarker for incipient AD.
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              The nuts and bolts of low-level laser (light) therapy.

              Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term "low level laser therapy" or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.
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                Author and article information

                Journal
                Reviews in the Neurosciences
                Walter de Gruyter GmbH
                2191-0200
                0334-1763
                April 28 2020
                April 28 2020
                : 31
                : 3
                : 269-286
                Affiliations
                [1 ]Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran
                [2 ]NiraxxLight Therapeutics, Irvine, CA 92617, USA
                [3 ]ProNeuroLIGHT LLC, 3504 W Buckhorn Trail, Phoenix, AZ 85083, USA
                [4 ]Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway H91 W2TY, Ireland
                [5 ]Department of Biomedical Engineering, Wrocław University of Science and Technology, Wrocław 50-370, Poland
                [6 ]Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA
                [7 ]Department of Dermatology, Harvard Medical School, 40 Blossom St, Boston, MA 02114, USA
                [8 ]Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
                [9 ]Neuropathy Treatment Centers of America LLC, Phoenix, AZ, USA
                [10 ]Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA
                [11 ]Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Bowdoin Square, Boston, MA 02114, USA
                [12 ]Center for Anxiety and Traumatic Stress Disorders, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
                Article
                10.1515/revneuro-2019-0063
                31812948
                d466949c-006c-4c06-a255-6ad4bae52570
                © 2020
                History

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