Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders

Abstract

Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopted in clinical practice for CNS injury or disease for a number of reasons, which include the following. The mechanism/s of action and implications of penetration have not been thoroughly addressed. The large range of treatment intensities, wavelengths and devices that have been assessed make comparisons difficult, and a consensus paradigm for treatment has not yet emerged. Furthermore, the lack of consistent positive outcomes in randomised controlled trials, perhaps due to sub-optimal treatment regimens, has contributed to scepticism. This review provides a balanced précis of outcomes described in the literature regarding treatment modalities and efficacy of R/NIR-IT for injury and disease in the CNS. We have addressed the important issues of specification of treatment parameters, penetration of R/NIR irradiation to CNS tissues and mechanism/s, and provided the necessary detail to demonstrate the potential of R/NIR-IT for the treatment of retinal degeneration, damage to white matter tracts of the CNS, stroke and Parkinson's disease.

Differential Effects of 670 and 830 nm Red near Infrared Irradiation Therapy: A Comparative Study of Optic Nerve Injury, Retinal Degeneration, Traumatic Brain and Spinal Cord Injury

“…However, R/NIR-IT has not been widely adopted in clinical practice for CNS injury, in part due to the large range of treatment fluences, irradiation time, wavelengths and devices cited in the literature making comparisons between studies difficult. As such, a consensus paradigm for treatment has not yet been established[48]. Here we report the outcomes of a multi-centre comparative study which shows that delivery of a defined number of photons at the surface of the skin overlying a CNS injury has differential effects on function and neuroprotection (as indicated by Tunel staining), depending upon the wavelength used to deliver the R/NIR-IT and the injury type.…”

“…Irradiation between 600 and 1000 nm has better penetration because of reduced absorption at these wavelengths [48]. We demonstrate here that while the 830 nm R/NIR-IT array delivered an equal quantal dose to the surface of the skin (5.33×10 16 photons cm −2 s −1 ), the number of photons received at the SCI injury site was greater due to the increased penetrance of the longer wavelength R/NIR-IT through tissue (6.0×10 15 photons cm −2 s −1 for the 830 nm device compared to 3.5×10 15 photons cm −2 s −1 for the 670 nm device).…”

“…However, given that efficacy was demonstrated in visual system models where animals were handled similarly, we consider this to be unlikely. It is perhaps more likely that the degree of inflammatory involvement, vascular changes, cyst formation, oedema and myelination [70]–[72] are likely to alter penetrance of the R/NIR-IT [48], [73] and may explain the lack of efficacy following SCI at the current comparatively low dosage. The moderate contusion SCI may be too severe an injury to enable detection of modest improvements at the doses of R/NIR-IT employed in the current study.…”

“…The therapeutic dose can be defined by the number of photons interacting with the photoacceptor (chromophore). As the energy of a photon varies with its wavelength, intensities of irradiation can be adjusted to ensure delivery of equal numbers of photons to provide an effective comparison of the efficacy of R/NIR-IT of different wavelengths [48]. We have conducted a multi-centre study designed to compare efficacy of equal numbers of photons of 670 nm and 830 nm R/NIR-IT, delivered to the surface of the skin overlying injury sites using LED arrays, in four models of CNS injury, each of mild to moderate severity: 1) in a model of secondary degeneration following partial injury to the optic nerve; 2) in light-induced retinal degeneration; 3) in traumatic brain injury (TBI) induced by fluid percussion impact; and 4) following a moderate contusion spinal cord injury (SCI).…”

A safety and feasibility study of the use of 670 nm red light in premature neonates

“…35 There are currently 10 randomized clinical trials registered with the WHO International Clinical Trials Registry ranging from treating back pain, stroke and traumatic brain injury. Near-infrared therapy has been used in a number of smaller studies with no adverse effects and most recently has been shown to increase peripheral blood flow, 36 reduce osteoarthiritis in knee joints 37 and improve wound healing in chronic diabetic foot ulcers.…”