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Correspondence to Author: Jermic Aryee, Abanoub Awadalla, Amar Bhigroog, Belinda Williams†, Lissa Alcius, Foday Kanu, Rana Zeine. 

Rana Zeine, Department of Biological Sciences, Kean University, Union, NJ 07083 USA; and Chamberlain University College of Nursing, North Brunswick, NJ 08902 USA
Jermic Aryee, Department of Biological Sciences, Kean University, Union, NJ, USA
Abanoub Awadalla, Amar Bhigroog, Belinda Williams†, Lissa Alicius, Foday Kanu, Saint James School of Medicine, St. Vincent Campus, Park Ridge, IL, USA

DOI: 10.52338/conr.2024.4088

Abstract:

Background : Chronic traumatic encephalopathy (CTE) is a progressive neurodegeneration that can be widely distributed throughout the brain due to accumulation of neuropathologic lesions following exposure to repetitive head impact (RHI) causing concussions or sub-concussive traumatic brain injury (TBI). Populations at risk include military personnel and contact sports athletes. A neuropathological severity staging system has been developed based on lesion complexity.
Aim : To systematically review the clinicopathologic correlations and neuroimmunologic mechanisms in CTE.
Methods : We conducted a systematic review by literature search through WorldCat.org and ProQuest Central, inclusive of PubMed and EBSCOhost electronic databases, to identify studies on CTE published between 2013 and 2023 in the English language. PubMed was last accessed on 25 January 2024.
Results : A total of 29 articles, 6 experimental and 23 human studies, were included from the US, Canada, Mexico, Germany, Italy, and the UK. Studies accessed brain tissues from the Veterans Affairs–Boston University–Concussion Legacy Foundation (VA–BU–CLF)/ Understanding Neurological Injury and Traumatic Encephalopathy (UNITE) brain bank, the Farmington Heart Study, and the Dublin brain bank. Severity of CTE progression was linked to player position and years played. Neuropathology included brain atrophy in the hippocampus, amygdala, frontal and temporal cortex, phosphorylated-tau (p-tau) neurofibrillary tangles, beta-amyloid plaques, thread and dot-like neurites, demyelination, axonal loss and Lewy bodies. A higher repetitive head injury index correlated with higher axial diffusivity on brain imaging, most severe in the corpus callosum CC1 area. Evidence of neuroinflammation included microglial activation, expression of pro-inflammatory markers, and lymphocyte trafficking of CD4+ helper-T cells followed by CD8+ cytotoxic T cells.
Conclusion : In CTE, neurodegeneration is most likely triggered by immune activation in response to brain tissue damage. Persistent neuroinflammation can perpetuate injury to both neurons and oligodendrocytes, resulting in concurrent neurodegeneration and demyelination. It is urgent that preventive measures be implemented to protect against dementia and neuropsychiatric decline. Recommendations include the use of padded helmets, testing for biomarkers such as Neurofilament Light, monitoring Cumulative Head Impact Index, supportive treatments for associated Post-Traumatic Stress Disorder (PTSD), and education. Further research could identify targetable molecular mechanisms, quantify traumatic load, and test pharmacologic treatment strategies.

Citation:

Rana Zeine. Elucidating Mechanisms of Chronic Traumatic Encephalopathy (CTE); A Systematic Review of the Literature.. Clinics of Neurology 2024.