Transcranial Photobiomodulation (Light) Therapy in Chronic Traumatic Encephalopathy (CTE)

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) represents a progressive tauopathy characterized by distinct neuropathological features following repetitive mild traumatic brain injury. Recent advances in photobiomodulation (PBM) therapy demonstrate significant potential in addressing the complex pathophysiology of CTE through targeted cellular mechanisms. This comprehensive review examines the clinical evidence, molecular pathways, and therapeutic protocols for implementing medical-grade light therapy in CTE management.

Introduction: The Pathophysiology of CTE

Chronic Traumatic Encephalopathy is a distinct neurodegenerative disease first described by Martland in 1928 as "punch drunk syndrome." The condition is characterized by the progressive accumulation of hyperphosphorylated tau protein in neurons and astrocytes, particularly 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 astrocytesSecondary Features: Neuroinflammation, axonal loss, white matter degeneration, and cerebral atrophyAnatomical Distribution: Frontal and temporal cortices, hippocampus, amygdala, and brainstem nucleiStaging Classification: McKee criteria stages I-IV based on anatomical spread and severity

The pathogenesis involves complex cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation—all potential targets for photobiomodulation intervention.

Molecular Mechanisms of Photobiomodulation in Neurodegeneration

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

Mechanism of Action:

Primary Photoacceptor: Cytochrome c oxidase (Complex IV) absorption peaks at 665nm, 750nm, and 830nmCellular Response: Increased ATP synthesis, enhanced mitochondrial membrane potential, and improved cellular respirationSecondary Signaling: Activation of transcription factors (NF-κB, AP-1), increased nitric oxide bioavailability, and modulation of reactive oxygen species

Specific Neurological Benefits:

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

Clinical Evidence in Traumatic Brain Injury and Neurodegenerative Conditions

Preclinical Studies:

Xuan et al. (2013) demonstrated that 810nm laser therapy significantly reduced tau hyperphosphorylation in a mouse model of repetitive mild TBI, directly addressing CTE's primary pathological feature. The study showed 60% reduction in p-tau immunoreactivity in treated animals compared to controls.

Chao et al. (2019) reported that transcranial PBM (1064nm) improved cognitive performance and reduced neuroinflammation markers in aged mice with tau pathology, suggesting direct relevance to CTE treatment.

Human Clinical Trials:

Traumatic Brain Injury Studies:

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

Neurodegenerative Disease Research:

• Saltmarche et al. (2017): Transcranial and intranasal PBM improved cognition in dementia patients, with neuroimaging showing increased cortical perfusion
• Michalikova et al. (2008): 670nm light therapy reduced amyloid-β plaques and improved memory in transgenic Alzheimer's models

Medical-Grade Photobiomodulation Protocols for CTE

Device Specifications:

Wavelength Selection:

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

Power Density Parameters:

• Therapeutic range: 10-200 mW/cm²
• Treatment dose: 1-20 J/cm²
• Pulse parameters: Continuous wave or 10-40Hz pulsing for enhanced penetration

Clinical Treatment Protocols:

Transcranial Application:

• Target areas: Frontal, temporal, and parietal regions
• Treatment duration: 20-30 minutes per session
• Frequency: Daily treatments for acute intervention, 3-5x weekly for maintenance
• Total treatment course: Minimum 4-6 weeks for initial response assessment

Intranasal Photobiomodulation:

• Wavelength: 810-830nm
• Power: 25-50mW total output
• Duration: 25 minutes per session
• Advantage: Direct access to brain via trigeminal and olfactory pathways

Patient Selection Criteria:

Inclusion Criteria:

• Documented history of repetitive head trauma
• Clinical symptoms consistent with CTE (cognitive, behavioral, motor)
• Stable medical condition
• No contraindications to light therapy

Exclusion Criteria:

• Active malignancy in treatment area
• Photosensitizing medications
• Severe psychiatric instability
• Concurrent use of photodynamic therapy

Advanced Neuroimaging and Biomarker Assessment

Neuroimaging Protocols:

Structural MRI: Assessment of cortical thinning, white matter integrity (DTI), and volumetric changesFunctional MRI: Evaluation of default mode network connectivity and task-related activation patternsPET Imaging: Tau-PET (18F-flortaucipir) for direct visualization of tau pathologySPECT: Regional cerebral blood flow assessment pre- and post-treatment

Biomarker Monitoring:

CSF Biomarkers:

• Total tau and phosphorylated 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 demonstrates an excellent safety profile with minimal adverse events reported in clinical trials. The non-invasive nature and absence of systemic effects make it particularly suitable for long-term therapeutic protocols.

Reported Adverse Events:

• Mild headache (2-5% of patients)
• Temporary visual disturbances during treatment
• Rare cases of mood changes during initial treatment phase

Absolute Contraindications:

• Pregnancy (precautionary)
• Active epilepsy or seizure disorders
• Malignancy in treatment area
• Concurrent photosensitizing drug therapy

Integration with Conventional CTE Management

Photobiomodulation therapy should be integrated as part of a comprehensive CTE management strategy:

Multidisciplinary Approach:

• Neurology: Primary diagnosis and medical management
• Neuropsychology: Cognitive assessment and rehabilitation
• Psychiatry: Management of mood and behavioral symptoms
• Physical Medicine: Motor symptom management and rehabilitation
• Photobiomodulation Specialist: Treatment protocol optimization

Adjunctive Therapies:

• Cognitive behavioral therapy
• Physical rehabilitation
• Nutritional optimization (omega-3 fatty acids, antioxidants)
• Sleep hygiene and optimization
• Pharmacological interventions as indicated

Future Directions and Research Priorities

Emerging Research Areas:

Combination Therapies: Investigation of PBM with neuroprotective agents, stem cell therapy, or transcranial stimulationPersonalized Medicine: Genetic markers (APOE status, tau genetics) for treatment response predictionAdvanced Protocols: Pulsed light parameters, novel wavelength combinations, and targeted delivery systemsLong-term Studies: Extended follow-up for disease modification assessment

Clinical Trial Priorities:

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

Conclusion

Photobiomodulation therapy represents a promising, evidence-based intervention for Chronic Traumatic Encephalopathy management. The therapy's ability to target fundamental pathogenic mechanisms—mitochondrial dysfunction, neuroinflammation, and cellular energy metabolism—positions it as a valuable adjunct to conventional CTE treatment protocols.

The growing body of clinical evidence, combined with the excellent safety profile and non-invasive nature, supports the integration of medical-grade photobiomodulation into comprehensive CTE care pathways. Healthcare providers should consider PBM therapy as part of a multidisciplinary approach to CTE management, with careful attention to proper patient selection, protocol optimization, and outcome monitoring.

As our understanding of CTE pathophysiology continues to evolve, photobiomodulation therapy offers a scientifically-grounded approach to addressing this challenging neurodegenerative condition, potentially improving quality of life for affected individuals and their families.

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