Candidate Molecular Biomarkers of Traumatic Brain Injury: A Systematic Review

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability among young and middle-aged individuals. Adequate and timely diagnosis of primary brain injuries, as well as the prompt prevention and treatment of secondary injury mechanisms, significantly determine the potential for reducing mortality and severe disabling consequences. Therefore, it is crucial to have objective markers that indicate the severity of the injury. A number of molecular factors-proteins and metabolites-detected in the blood immediately after trauma and associated with the development and severity of TBI can serve in this role. TBI is a heterogeneous condition with respect to its etiology, clinical form, and genesis, being accompanied by brain cell damage and disruption of blood-brain barrier permeability. Two oppositely directed flows of substances and signals are observed: one is the flow of metabolites, proteins, and nucleic acids from damaged brain cells into the bloodstream through the damaged blood-brain barrier; the other is the infiltration of immune cells (neutrophils and macrophages) and serological proteins. Both flows aggravate brain tissue damage after TBI. Therefore, it is extremely important to study the key signaling events that regulate these flows and repair the damaged tissues, as well as to enhance the effectiveness of treatments for patients after TBI.