Chronic traumatic encephalopathy: Diagnostic updates and advances

Abstract

<abstract> <p>Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs secondary to repetitive mild traumatic brain injury. Current clinical diagnosis relies on symptomatology and structural imaging findings which often vary widely among those with the disease. The gold standard of diagnosis is post-mortem pathological examination. In this review article, we provide a brief introduction to CTE, current diagnostic workup and the promising research on imaging and fluid biomarker diagnostic techniques. For imaging, we discuss quantitative structural analyses, DTI, fMRI, MRS, SWI and PET CT. For fluid biomarkers, we discuss p-tau, TREM2, CCL11, NfL and GFAP.</p> </abstract>

Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract

“…An increase in autoantibodies against neuronal and glial antigens is part of a pathological process observed in several neurodegenerative diseases and with brain injury and exacerbates the damage to the nervous system 10,11,28,89–93 . However, when autoantibody production is elicited by antigens delivered in food, the immune response can be suppressed through an oral tolerance mechanism, which involves initial production of IgM antibodies against given antigens and later transition to production of IgG antibodies against the same antigens, which can confer long‐term suppression of the immune response 94,95 .…”

“…An increase in autoantibodies against neuronal and glial antigens is part of a pathological process observed in several neurodegenerative diseases and with brain injury and exacerbates the damage to the nervous system. 10,11,28,[89][90][91][92][93] However, when autoantibody production is elicited by antigens delivered in food, the immune response can be suppressed through an oral tolerance mechanism, which involves initial production of IgM antibodies against given antigens and later transition to production of IgG antibodies against the same antigens, which can confer long-term suppression of the immune response. 94,95 When antigens delivered in food are identical or highly homologous to those that are normally not present in circulation at high levels and are released from the brain tissues upon injury, the circulating IgG antibodies induced through ingestion of food would prevent the immune system attack on cells that carry those antigens, thus reducing inflammation.…”

“…This is particularly relevant to repetitive mild traumatic brain injury (mTBI) and consequent CTE because the immune system is activated continuously due to repeated BBB disruption and cascades of cytotoxic events. 10,11,28,29 However, when autoantibodies are induced in response to antigens present in food, the immune response against these food-derived antigens in most cases can be suppressed through an oral tolerance mechanism. [30][31][32][33] In fact, induction of immune tolerance is one of the proposed novel approaches toward treating neurodegenerative diseases, TBI, and also surgical brain injury, where delivery of nervous system antigens through oral, nasal mucosa or intravenous routes was shown to reduce inflammation and offer neuroprotection.…”

“…Approximately 5 million people in the United States (U.S.) alone suffer from the lasting consequences of this injury. [7][8][9] TBI, including mild repetitive TBI, is one of the most significant non-genetic and non-agerelated risk factors for neurodegenerative diseases, such as chronic traumatic encephalopathy (CTE), 10,11 Alzheimer's disease (AD), AD-like dementias, 5,[12][13][14][15] and even brain cancer. 16 The consequences of TBI, however, extend well beyond the brain health and cognitive function and affect other organ systems.…”

“…Circulating IgG antibodies against neuronal and glial antigens may also indicate neurodegenerative disease, nervous system injury, and inflammatory response, where the damage to the BBB, combined with the breakdown of cells and tissues containing neuronal and glial peptides, contributes to poor recovery from the injury and exacerbates neurological sequelae. This is particularly relevant to repetitive mild traumatic brain injury (mTBI) and consequent CTE because the immune system is activated continuously due to repeated BBB disruption and cascades of cytotoxic events 10,11,28,29 . However, when autoantibodies are induced in response to antigens present in food, the immune response against these food‐derived antigens in most cases can be suppressed through an oral tolerance mechanism 30–33 .…”