Biomarkers of focal and diffuse traumatic brain injury

In the previous issue of Critical Care, Mondello and colleagues [1] demonstrate that easy to obtain biochemical markers of brain injury in peripheral blood may complement current predictors of outcome in severe traumatic brain injury (TBI). The study also advocates that use of biomarkers may contribute to better understanding of the pathophysiological mechanisms of brain damage. After TBI, brain tissue-specific neuronal and glial proteins may suddenly appear in the systemic circulation via leakage through the disturbed blood brain barrier or via leakage to the cerebrospinal fluid and subsequent normal transport to the circulation. Despite the strength of the association between existing predictors of outcome, the prognostic value is still modest. Studies in more than 10,000 patients demonstrate a diagnostic accuracy of 0.70 to 0.84, which is insufficient as a diagnostic and prognostic tool in individual patients [2,3]. Current models explain only 35% of the outcome variation [4]. Considering the large proportion of outcome variation that remains unexplained, the models need to be refined [5].Mondello and colleagues determined in a cohort of 81 severe TBI patients the time course of neuronal (ubiquitin carboxy-terminal hydrolase (UCH)-L1) and astroglial (glial fibrillary acidic protein (GFAP)) biomarker levels in serum in the first 24 hours after severe focal and diffuse injuries. UCH-L1 and GFAP were selected because of abundant expression in neurons (UCH-L1) and astrocytes (GFAP). UCH-L1 is involved in the addition or removal of ubiquitin from abnormal proteins destined for proteasomal degradation and has previously been used as a neuronal cell soma marker [6]. Initial results in cerebrospinal fluid showed higher levels of UCH-L1 in patients with low Glasgow Coma Scale (GCS) scores, post-injury complications, early mortality and poor 6-month outcome. GFAP was chosen because of its high specificity for central nervous system astrocytes and its strong association wit