Photobiomodulation Therapy and the Glymphatic System: Promising Applications for Augmenting the Brain Lymphatic Drainage System.

The glymphatic system is a glial-dependent waste clearance pathway in the central nervous system, devoted to drain away waste metabolic products and soluble proteins such as amyloid-beta. An impaired brain glymphatic system can increase the incidence of neurovascular, neuroinflammatory, and neurodegenerative diseases. Photobiomodulation (PBM) therapy can serve as a non-invasive neuroprotective strategy for maintaining and optimizing effective brain waste clearance. In this review, we discuss the crucial role of the glymphatic drainage system in removing toxins and waste metabolites from the brain. We review recent animal research on the neurotherapeutic benefits of PBM therapy on glymphatic drainage and clearance. We also highlight cellular mechanisms of PBM on the cerebral glymphatic system. Animal research has shed light on the beneficial effects of PBM on the cerebral drainage system through the clearance of amyloid-beta via meningeal lymphatic vessels. Finally, PBM-mediated increase in the blood-brain barrier permeability with a subsequent rise in Aß clearance from PBM-induced relaxation of lymphatic vessels via a vasodilation process will be discussed. We conclude that PBM promotion of cranial and extracranial lymphatic system function might be a promising strategy for the treatment of brain diseases associated with cerebrospinal fluid outflow abnormality.

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

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.

Rapid Reversal of Cognitive Decline, Olfactory Dysfunction, and Quality of Life Using Multi-Modality Photobiomodulation Therapy: Case Report.

Objective: We present a case report of reversal of cognitive impairment, olfactory dysfunction, and quality of life measures in a patient with cognitive decline after multi-modality photobiomodulation (PBM) therapy. Background: Transcranial and intranasal PBM has been introduced as a light-based therapeutic technique in which exposure to low levels of red to near-infrared (NIR) light stimulates neuronal function, leading to beneficial neurological effects. Materials and methods: Patient received twice-daily PBM therapy at home using three different wearable light-emitting diode (LED) devices. For the first week containing a mixture of continuous wave mode red (635 nm) and NIR (810 nm) LEDs, a prototype transcranial light helmet and a body pad were used. The body pad was placed on various areas on the lower back and the helmet was worn while seated. After the first week of treatment, an intranasal LED device, 10-Hz pulsed wave mode NIR (810 nm), was initiated in the left nostril twice daily. All three devices were applied simultaneously for an irradiation time of 25 min per session. Results: The patient showed a significant improvement in the Montreal Cognitive Assessment score from 18 to 24 and in the Working Memory Questionnaire score from 53 to 10. The cognitive enhancement was accompanied by reversal of olfactory dysfunction as measured by the Alberta Smell Test and peanut butter odor detection test. Quality-of-life measures improved and caregiver stress was reduced. No adverse effects were reported. Conclusions: PBM therapy may be a promising noninvasive approach for patients with neurodegenerative diseases.