Scientists have discovered that transcranial infrared light therapy can promote tissue repair after mild traumatic brain injury (mTBI). In animal studies, brief daily infrared treatments for four weeks reduced harmful inflammatory activity and cell death in the brain after injury. This research may pave the way for a new therapeutic option for mTBI, where treatments are limited.
Traumatic brain injury (TBI) is a significant global health problem and a common cause of death and disability, particularly in young people.
While the consequences of moderate and severe injuries can be profound, even mild injuries often result in persistent disabling symptoms.
Of those injured, more than 50% report ongoing symptoms that persist for more than 6 months after the injury, including headaches, depression, cognitive symptoms, and balance problems.
Despite the clinical need for interventions to improve recovery, no effective disease-modifying therapies have been identified to control the range of post-injury responses and prevent secondary brain tissue injury and subsequent cell damage/loss.
Prospective therapeutics for TBI must successfully intervene on a multitude of pathophysiological mechanisms to influence patient outcome.
Photobiomodulation (PBM) is an optical therapy based on the administration of red or near-infrared light (600–1000 nm) for a therapeutic effect.
The light is absorbed by cytochrome c oxidase, a mitochondrial protein important for cellular energy production. This process helps stabilize mitochondria (the cells’ powerhouses) and reduce oxidative stress—the accumulation of free radicals that are harmful to cells.
In addition, PBM appears to help protect against cell death by modulating cellular pathways that prevent apoptosis (programmed cell death). It also reduces the activation of immune cells called microglia, which, when overactivated after a TBI, contribute to increased brain inflammation.
Preclinical research, conducted in animal models, has shown that PBM administered shortly after TBI helps rat brains recover and reduces signs of inflammation and oxidative stress.
Furthermore, early human clinical studies indicate that PBM can alleviate functional and emotional symptoms in patients undergoing rehabilitation after TBI.
To ensure that PBM is effective, certain parameters need to be defined, such as the wavelength, time of treatment initiation, and duration of sessions.
Study results indicate that PBM is most effective when used with wavelengths of 660 nm (red) and 810 nm (near infrared), with treatment starting within the first four hours after injury and lasting up to three days.
These parameters appear to optimize the beneficial effects of PBM, promoting brain recovery.
A new study, published in Bioengineering and Translational Medicine by researchers at the University of Birmingham, aimed to (1) validate the delivery of PBM in the 20–40 mW/cm2 range to the cortical surface of the rat brain using ex vivo modeling; and (2) evaluate the efficacy of various PBM wavelengths to promote functional and histological recovery after TBI.
In this study, the scientists first optimized PBM delivery parameters for use in mTBI by conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface.
They then used an in vivo weight-drop mTBI model in adult rats and administered optimized daily doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, while histology and immunohistochemistry were used to assess the neuropathology of mTBI.
After analyzing the results, they observed that daily treatment with 660, 810 nm light, or a combination of the two, resulted in significant improvements in memory and coordination tests in the animals.
Histology did not demonstrate any evident structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b+ microglia and glial fibrillary acidic protein (GFAP)+ astrocytes at 3 days post-injury. This suggests a reduced inflammatory response.
Significantly reduced cortical localization of the cell death marker (cleaved caspase-3) and modest reductions in extracellular matrix deposition were also observed after PBM treatment, limited to the choroid plexus and periventricular areas.
This suggests less cell loss with treatment. The effects of PBM are promising for the recovery of cognitive and motor functions in patients with TBI. In particular, 810 nm light has shown the greatest tissue penetration, being more effective in reaching deeper layers of the brain.
PBM also appears to have the potential to treat other related neurodegenerative diseases, such as Alzheimer's, by reducing the formation of tau proteins, which accumulate in some neurodegenerative conditions.
In summary, photobiomodulation presents itself as an emerging therapy for treating traumatic brain injuries and their long-lasting effects, but more research is still needed to define optimal clinical protocols and demonstrate the safety and efficacy of the technique in humans.
These studies represent a step forward in the understanding and treatment of brain injuries, especially in cases where therapeutic options are limited.
PBM results in reduced cortical expression of cleaved caspase-3 at 3 days post-injury. (a) Comparison of cleaved caspase-3+ nuclei counts in five cortical areas. (b) Comparison of whole-field cleaved caspase-3 fluorescence intensity in five cortical areas. (c) Immunofluorescence imaging in area HL. A total of 660 and/or 810 nm were used in the PBM group (2 min per day (1 min per hemisphere)). n = 4 per group. AU, arbitrary units; CC3, cleaved caspase-3; DAPI, 4,6-diamidino-2-phenylindole; ns, not significant; PBM, photobiomodulation; TBI, traumatic brain injury.
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Photobiomodulation improves functional recovery after mild traumatic brain injury
Andrew R. Stevens, Mohammed Hadis, Abhinav Thareja, Freya G. Anderson, Michael R. Milward, Valentina Di Pietro, Antonio Belli, William Palin, David J. Davies, Zubair Ahmed
Bioeng Transl Med. 2024; e10727. 11 October 2024
Abstract:
Mild traumatic brain injury (mTBI) is a common consequence of head injury but there are no recognized interventions to promote recovery of the brain. We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660 nm, or 810/660 nm all significantly improved both NOR and beam balance performance, with 810 nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b+ microglia and glial fibrillary acidic protein (GFAP)+ astrocytes at 3 days post-injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase-3, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810 nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte/microglial activation, and thus may be useful as a potential regenerative therapy.
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