Abstract
The onset of concussive head trauma often triggers an intricate sequence of physical consequences and pathophysiological responses. These sequelae can be acute (i.e., hematoma) or chronic (i.e., autoimmune response, neurodegeneration, etc.), and may follow traumas of any severity. A critical factor for prognostication of postconcussion outcome is the pathophysiological response of cellular barriers, which can be measured by several biomarkers of the acute and chronic postinjury phases. We present herein a review on the postconcussion mechanisms of the blood–brain barrier, as well as the diagnostic/prognostic approaches that utilize differential biomarker expression across this boundary. We discuss the role of the blood–saliva cellular barrier as a regulatory filter for brain-derived biomarkers in blood, and its implications for saliva-based diagnostic assays.
Highlights
An emerging method for postinjury assessment is the observation of differential expression of brain-derived biomarkers across cellular barriers of the body, which can be observed in blood and saliva
Author contributions D Janigro is a Professor at CWRU, a member of the World Neurobiology Commission of ILAE, and CSO/Founder of FloTBI, Inc. He has over 30 years of research experience and is the inventor of the dynamic in vitro model of the blood–brain barrier
He has patented S100B as a marker of BBB function and has for many years collaborated with top notch hospitals in the USA and Europe to broaden the scope and use of this technology
Summary
The glymphatic system as a source of markers of traumatic brain injury In addition to the endothelial–brain interface at the BBB, another potential pathway for markers’ extravasation has been recently proposed by Nedergaard’s group [19,20]. A common way to prevent autoimmunity is by hiding self-tissues behind a barrier impermeable to circulating immune cells. Another mechanism is the lack of significant entry of B lymphocytes in normal brain. Emerging data indicate that TBI activates B lymphocytes producing antibodies specific for antigen found within and outside the CNS. The plausibility of this autoimmune hypothesis is supported by multiple prior studies demonstrating a link between barrier disruption, autoantigen leakage, autoantibodies and autoimmune disease. The role & diagnostic significance of cellular barriers after concussive head trauma Review
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