New Prognostic Biomarkers in Patients With Traumatic Brain Injury

Context: Traumatic brain injury (TBI) is a leading cause of death, disability, and resource consumption per year. There are two kinds of brain injury in TBI, primary and secondary injuries. Primary injury refers to the initial physical forces applied to the brain at the moment of impact. Secondary injury occurs over a period of hours or days following the initial trauma and results from the activation of different pathways such as inflammation, coagulation, oxidation, and apoptosis. Evidence Acquisition: This review focuses on new prognostic biomarkers of mortality in TBI patients related to inflammation, coagulation, oxidation, and apoptosis. Results: Recently circulating levels of substance P (SP), soluble CD40 ligand (sCD40L), tissue inhibitor of matrix metalloproteinases (TIMP)1, malondialdehyde (MDA), and cytokeratin (CK)-18 fragmented have been found to be associated with mortality in TBI patients. Substance P is a neuropeptide of the tachykinin family, mainly synthesized in the central and peripheral nervous system, with proinflammatory effects when binding to their neurokinin-1 receptor (NK1R). Soluble CD40 ligand, a member of the tumor necrosis factor (TNF) family that is released into circulation from activated platelets, exhibit proinflamatory, and procoagulant properties on binding to their cell surface receptor CD40. Matrix metalloproteinases (MMPs) are a family of zinc-containing endoproteinases involved neuroinflammation and TIMP-1 is the inhibitor of some of them. Malondialdehyde is an end-product formed during lipid peroxidation due to degradation of cellular membrane phospholipids, that is released into extracellular space and finally into the blood. Cytokeratin -18 is cleaved by the action of caspases during apoptosis, and CK-18 fragmented is released into the blood. Conclusions: Circulating levels of some biomarkers, such as SP, sCD40L, TIMP-1, MDA, and CK-18 fragmented, related to inflammation, coagulation, oxidation, and apoptosis have been recently associated with mortality in patients with TBI. These biomarkers could help in the prognostic classification of the patients and open new research lines in the treatment of patients with TBI.