Abstract
Traumatic Brain Injury (TBI) and persistent post-concussion syndrome (PCS) including chronic migraine (CM) are major health issues for civilians and the military. It is important to understand underlying biochemical mechanisms of these conditions, and be able to monitor them in an accurate and minimally invasive manner. This study describes the initial use of a novel serum analytical platform to help distinguish TBI patients, including those with post-traumatic headache (PTH), and to help identify phenotypes at play in these disorders. The hypothesis is that physiological responses to disease states like TBI and PTH and related bodily stresses are reflected in biomolecules in the blood in disease-specific manner. Leave one out (serum sample) cross validations (LOOCV) and sample randomizations were utilized to distinguished serum samples from the following TBI patient groups: TBI +PTSD + CM + severe depression (TBI “most affected” group) vs healthy controls, TBI “most affected” vs TBI, TBI vs controls, TBI + CM vs controls, and TBI + CM vs TBI. Inter-group discriminatory p values were ≤ 10−10, and sample group randomizations resulted in p non-significant values. Peptide/protein identifications of discriminatory mass peaks from the TBI “most affected” vs controls and from the TBI plus vs TBI minus CM groups yielded information of the cellular/molecular effects of these disorders (immune responses, amyloidosis/Alzheimer’s disease/dementia, neuronal development). More specific biochemical disease effects appear to involve blood brain barrier, depression, migraine headache, autoimmunity, and autophagy pathways. This study demonstrated the ability for the first time of a novel, accurate, biomarker platform to monitor these conditions in serum, and help identify biochemical relationships leading to better understanding of these disorders and to potential therapeutic approaches.
Highlights
Traumatic brain injury (TBI) is a major health issue for civilians and for the military
Much research in the Traumatic Brain Injury (TBI) and post-concussion syndrome (PCS) field is focused on identifying short-term changes associated with TBI, while less attention has been paid to the long-term effects on patients
By observing individuals 5–14 years after the initial TBI, this present study focuses on the longterm physiological changes of PCS potentially induced by the TBI
Summary
Traumatic brain injury (TBI) is a major health issue for civilians and for the military. TBI is often associated with the post-concussion syndrome (PCS) which can include chronic daily headache (CDH), post-traumatic stress disorder (PTSD), and/or depression, all of which are health concerns for both military personnel and civilians [5,6,7]. In patients with D-TBI and CM, the addition of PTSD and/or SDep make the headache severity worse and the diagnosis and treatment more complicated These observations indicate in studies of TBI and PTH (including CM), especially associated with deployed veterans, consideration should be given to these related factors (PTSD and/or SDep) in an effort to better understand TBI PCS patient symptoms and their persistence and potential biochemical/physiological inter-relationships
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