GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask

Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools.