Photobiomodulation Therapy for Chronic Traumatic Encephalopathy: A Comprehensive Medical Review

Abstract

On July 28, 2025, Shane Devon Tamura, a 27-year-old former high-school football player, carried out a mass shooting at 345 Park Avenue in Midtown Manhattan—a building that houses the NFL headquarters. In his three-page suicide note, Tamura blamed the NFL for his alleged CTE (“You can’t go against the NFL, they’ll squash you”) and pleaded, “Study my brain please.” He claimed football had caused CTE, even though he never played professionally and has not been diagnosed (CTE remains diagnosable only postmortem).

Chronic Traumatic Encephalopathy (CTE) is a progressive tauopathy characterized by distinct neuropathological features following repetitive mild traumatic brain injury. Recent studies suggest photobiomodulation (PBM) therapy may help address aspects of CTE pathophysiology through targeted cellular mechanisms. This review summarizes the clinical evidence, molecular pathways, and therapeutic protocols for medical-grade light therapy in CTE management.

Introduction: The Pathophysiology of CTE

Chronic Traumatic Encephalopathy is a neurodegenerative disease first described by Martland in 1928 as "punch drunk syndrome." It is marked by the progressive accumulation of hyperphosphorylated tau protein in neurons and astrocytes, especially in cortical sulci, around small blood vessels, and at the depths of cerebral sulci.

Neuropathological Hallmarks

Primary Pathology: Perivascular accumulation of phosphorylated tau (p-tau) in neurons and astrocytes
Secondary Features: Neuroinflammation, axonal loss, white matter degeneration, and cerebral atrophy
Anatomical Distribution: Frontal and temporal cortices, hippocampus, amygdala, and brainstem nuclei
Staging Classification: McKee criteria stages I–IV based on anatomical spread and severity

The pathogenesis involves cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation—each a potential target for photobiomodulation.

Molecular Mechanisms of Photobiomodulation in Neurodegeneration

Photobiomodulation uses specific wavelengths of light (typically 630–1000 nm) to modulate cellular function through photochemical processes. The primary chromophore is cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain.

This information is educational and not a substitute for professional medical advice.

Mechanism of Action:

Primary Photoacceptor: Cytochrome c oxidase (Complex IV) absorbs light at 665 nm, 750 nm, and 830 nm.
Cellular Response: Increased ATP synthesis, higher mitochondrial membrane potential, and improved cellular respiration.
Secondary Signaling: Activation of transcription factors (NF-κB, AP-1), greater nitric oxide availability, and modulation of reactive oxygen species.

Specific Neurological Benefits:

1. Mitochondrial Biogenesis: Up-regulation of PGC-1α and subsequent mitochondrial proliferation.
2. Neuroprotection: Inhibition of apoptotic pathways and preservation of neuronal integrity.
3. Anti-inflammatory Effects: Lower levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6).
4. Vascular Effects: Improved cerebral blood flow and blood-brain barrier integrity.
5. Neuroplasticity: Enhanced BDNF expression and synaptic plasticity.

Clinical Evidence in Traumatic Brain Injury and Neurodegenerative Conditions

Preclinical Studies:

Xuan et al. (2013) reported that 810 nm laser therapy markedly reduced tau hyper-phosphorylation in a mouse model of repetitive mild TBI, a key feature of CTE pathology; treated animals showed a 60 % drop in p-tau immunoreactivity versus controls.

Chao et al. (2019) found that transcranial PBM at 1 064 nm improved cognition and lowered neuro-inflammation markers in aged mice with tau pathology, suggesting potential relevance for CTE.

Human Clinical Trials:

Traumatic Brain Injury Studies:

• Henderson et al. (2015): Transcranial LED therapy (635 nm / 870 nm) produced significant cognitive gains in 68 chronic TBI patients over 12 weeks.
• Bogdanova et al. (2020): Near-infrared therapy improved attention and executive function in military veterans with a history of TBI.

Neurodegenerative Disease Research:

• Saltmarche et al. (2017): Transcranial and intranasal PBM improved cognition in dementia patients; neuro-imaging revealed increased cortical perfusion.
• Michalikova et al. (2008): 670 nm light therapy reduced amyloid-β plaques and improved memory in transgenic Alzheimer’s models.

Medical-Grade Photobiomodulation Protocols for CTE

Device Specifications:

Wavelength Selection:

 Further reading:  

   
• PubMed database
   
• ClinicalTrials.gov registry
 

• 660-670 nm (red): superficial tissue penetration, strong CCO absorption
• 810-830 nm (near-infrared): deep tissue penetration, optimal brain targeting
• 1064 nm (infrared): greatest penetration depth, minimal scattering

Power Density Parameters:

• Therapeutic window: 10–200 mW/cm²
• Treatment dose: 1–20 J/cm²
• Pulse mode: continuous wave or 10–40 Hz pulsing for deeper reach

Clinical Treatment Protocols:

Transcranial Application:

• Target areas: frontal, temporal, and parietal regions
• Session length: 20–30 min
• Frequency: daily for acute care, 3–5×/week for maintenance
• Initial course: ≥4–6 weeks before first response check

Intranasal Photobiomodulation:

• Wavelength: 810–830 nm
• Power: 25–50 mW total output
• Duration: 25 min per session
• Advantage: direct access via trigeminal and olfactory routes

Patient Selection Criteria:

Inclusion Criteria:

• Documented repetitive head trauma
• Symptoms consistent with CTE (cognitive, behavioural, motor)
• Medically stable
• No light-therapy contraindications

Exclusion Criteria:

• Active malignancy in treatment field
• Photosensitising medication
• Severe psychiatric instability
• Concurrent photodynamic therapy

Advanced Neuroimaging and Biomarker Assessment

Neuroimaging Protocols:

Structural MRI: cortical thickness, white-matter integrity (DTI), volumetrics
Functional MRI: default-mode connectivity and task activation
PET Imaging: tau-PET (¹⁸F-flortaucipir) for tau pathology
SPECT: regional cerebral blood flow before and after treatment

Biomarker Monitoring:

CSF Biomarkers:

• Total tau, p-tau (T181, T231)
• Neurofilament light chain (NfL)
• Inflammatory markers (YKL-40, sTREM2)

Blood Biomarkers:

• Plasma tau species
• GFAP (glial fibrillary acidic protein)
• UCH-L1 (ubiquitin C-terminal hydrolase L1)

Safety Profile and Contraindications

Photobiomodulation shows a favorable safety record, with few adverse events reported in trials. Its non-invasive nature and lack of systemic effects make it suitable for extended protocols.

Reported Adverse Events:

 
• Mild headache (2–5% of participants)
 
• Transient visual disturbances during sessions
 
• Occasional mood changes early in treatment

Absolute Contraindications:

 
• Pregnancy (precautionary)
 
• Active epilepsy or seizure disorders
 
• Malignancy within the treatment field
 
• Concurrent photosensitizing medication

Integration with Conventional CTE Management

Photobiomodulation is best used within a comprehensive CTE care plan:

Multidisciplinary Approach:

 
• Neurology: primary diagnosis and medical oversight
 
• Neuropsychology: cognitive evaluation and rehabilitation
 
• Psychiatry: mood and behavioral symptom management
 
• Physical Medicine: motor symptom control and rehab
 
• Photobiomodulation Specialist: protocol design and monitoring

Adjunctive Therapies:

 
• Cognitive behavioral therapy
 
• Physical rehabilitation
 
• Nutritional support (omega-3s, antioxidants)
 
• Sleep hygiene training
 
• Pharmacotherapy when indicated

Future Directions and Research Priorities

Emerging Research Areas:

Combination Therapies: PBM paired with neuroprotective agents, stem-cell approaches, or transcranial stimulation.
Personalized Medicine: genetic markers such as APOE or tau variants to predict response.
Advanced Protocols: pulsed-light parameters, novel wavelength pairings, and targeted delivery.
Long-term Studies: extended follow-up to assess potential disease-modifying effects.

This information is educational and not a substitute for professional medical advice.

Clinical Trial Priorities:

 
• Randomized controlled trials specifically in CTE populations
 
• Dose-response relationship studies
 
• Biomarker-guided treatment protocols
 
• Health economic evaluations

Conclusion

Photobiomodulation therapy is a promising, evidence-informed option for managing Chronic Traumatic Encephalopathy. By potentially moderating mitochondrial dysfunction, neuroinflammation, and cellular energy deficits, it may complement standard CTE care.

An expanding set of small clinical studies, together with a generally favorable safety profile and non-invasive delivery, suggests PBM could be integrated into multidisciplinary CTE pathways when patient selection, dosing, and follow-up are carefully managed.

As understanding of CTE evolves, photobiomodulation remains a scientifically grounded candidate for easing disease burden, although larger trials are needed to confirm benefit.

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