Cerebrospinal Fluid as a Platform for Biomarker Identification in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a common cause for mortality and disability following severe head injury as well as milder concussive head injury. Despite high incidence and prevalence, no pharmacological treatments currently exist for TBI. Current research efforts aim to utilize existing pathophysiological data to derive therapeutic agents that can be utilized clinically. Of interest in this process are biofluid protein biomarkers of tissue fate – i.e., proteins that convey information that can be used as a surrogate for, e.g., injury severity or that can aid in patient prognostication. Traditionally, blood has been the biofluid of choice because of its accessibility. Yet, when it comes to the central nervous system, the biofluids in closer proximity with the brain are likely to be superior. As such, cerebrospinal fluid (CSF) is interesting, as it can be accessed either through an external ventricular drain in severely injured patients, or through a lumbar puncture for patients experiencing long-term sequelae following milder injuries. CSF naturally contains proteins, of likely importance following TBI. Numerous such proteins have been shown to be amenable to analysis using either exploratory or hypothesis-driven quantitative proteomic techniques. This has led to the discovery of important prognostic proteins following TBI, currently pointing toward neuroinflammation as a driver of cellular injury in the aftermath of TBI of potential importance both for development of therapeutics and for stratification of the individual patient. This chapter summarizes the field of protein biomarkers of tissue fate in CSF following predominantly severe TBI.