Clinical Science Session discussed biomarkers and surrogate markers in traumatic brain injury (TBI). Surrogate markers substitute for clinical endpoints and predict outcomes. Biomarkers objectively measure normal and pathological biological processes. Several potential biomarkers for TBI were discussed, including S-100β, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), cleaved tau, spectrin breakdown products (SBDPs), and apoptosis markers. However, none have been established as broadly accepted surrogate markers for acute brain injury. Further research is still needed to identify reliable biomarkers that predict outcomes and can be used to evaluate treatments early after TBI.
Clinical Science Session discussed biomarkers and surrogate markers in traumatic brain injury (TBI). Surrogate markers substitute for clinical endpoints and predict outcomes. Biomarkers objectively measure normal and pathological biological processes. Several potential biomarkers for TBI were discussed, including S-100β, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), cleaved tau, spectrin breakdown products (SBDPs), and apoptosis markers. However, none have been established as broadly accepted surrogate markers for acute brain injury. Further research is still needed to identify reliable biomarkers that predict outcomes and can be used to evaluate treatments early after TBI.
Clinical Science Session discussed biomarkers and surrogate markers in traumatic brain injury (TBI). Surrogate markers substitute for clinical endpoints and predict outcomes. Biomarkers objectively measure normal and pathological biological processes. Several potential biomarkers for TBI were discussed, including S-100β, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), cleaved tau, spectrin breakdown products (SBDPs), and apoptosis markers. However, none have been established as broadly accepted surrogate markers for acute brain injury. Further research is still needed to identify reliable biomarkers that predict outcomes and can be used to evaluate treatments early after TBI.
G1A218068 Surrogate markers: Surrogate or end point markers are intended to substitute for a clinical end point. They are expected to predict clinical benefit or harm (or lack of benefit or harm) based on epidemiological, therapeutic, pathophysiological, or other scientific evidence.
Biomarkers: A biomarker is a characteristic that is objectively measured and evaluated as an
indicator of normal biological processes, pathological processes, or responses to a therapeutic intervention. It should appear in easily accessible material such as blood or cerebrospinal fluid (CSF) and should be highly sensitive and specific.
Intention of using biomarkers or surrogate markers: The intention of using bio- or
surrogate markers is to get new insights into the pathophysiology of brain trauma, that is, the effects of therapeutic interventions as well as the chance of a sufficient and efficient evaluation of patient outcome after traumatic brain injury at early time points. • Evidence for efflux of brain proteins in humans was provided by reports showing that levels of certain neuronal and astroglial proteins are increased measurably in CSF or serum after TBI. • The most extensively studied markers are the astroglial protein S-100β, myelin basic protein (MBP), neuron-specific enolase (NSE), and a proteolytic fragment of the microtubule associated protein tau, called cleaved-tau (C-tau). • Unfortunately, high serum concentrations of those proteins have also been found with chronic disease unrelated to acute brain injury or even in its absence. • Not all kinds of brain injury occur with a measurable elevation in S-100β, MBP, NSE, or C-tau. • None of those proteins has been established as a broadly accepted surrogate marker for acute brain injury. S-100β Neuron-Specific Enolase (NSE) • NSE concentrations measured in CSF have served as markers of neuronal damage due to a variety of neurological disorders such as status epilepticus or Creutzfeldt-Jacob disease. • Elevated NSE levels are also found in the CSF and serum after TBI and were thus thought to be a possible surrogate marker for TBI. Glial Fibrillary Acidic Protein (GFAP) • Recent clinical studies revealed that GFAP is released to serum after TBI and the levels are related to trauma severity. • Pelinka’s studies clearly showed that GFAP serum levels were related to the extent of brain damage, and that different patterns of TBI seemed to beassociated with differences in GFAP release. They finally found that GFAP is a strong predictor in mortality and correlated well with severe disability and vegetative state. Cleaved Tau • After experimental TBI are missing so far. Instead, histological assessment of lesion size and tissue loss is used to calculate trauma severity and the efficacy of neuroprotective drugs in experimental TBI. On the other hand, surrogate markers should also be potentially clinically applicable. Previous biomarkers NSE and S- 100- have failed to fulfill both requirements. Spectrin Breakdown Products (SBDPs) • Despite the fact that focal and diffuse brain injuries can be evoked by different mechanisms, several studies to date have shown that similar biochemical cascades take part in the pathobiology of these different injury types. • SBDP immunoblots provide concurrent information about calpain76 and caspase-388 activation, two of the most important regulators of cell death after TBI, thus offering interesting insight into the pathobiochemical mechanisms of trauma. Moreover, as the characteristic spectrin-derived products appear in easy accessible material, this may lead to a better monitoring of the progression of damage, response to medical intervention, and even prediction of patient outcome, thus making SSDPs a potential bio- and surrogate marker for TBI. Apoptosis Marker • The initial tissue injury of the brain is proportional to the primary impact; however, recent studies suggest that acute and chronic cell death after TBI may also be due to PCD or apoptosis. • There is an increasing amount of PCD markers but we focused on those molecules that give the most useful insights in brain pathology after TBI and that allow determination of biopathological pathways. Caspase-3 as effector, the pro-apoptotic Fas, or bcl-2 as a potential antiapoptotic agent seem to be the most valuable candidates in this group of biomarkers. The parallel increase of these three molecules may indicate that PCD plays a pivotal role in posttraumatic cell loss and edema and emphasize the significance of apoptosis markers as potential bio/surrogate markers for TBI.