Blood biomarkers for brain injury: What are we measuring?

Abstract

Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury.

S100β in newborns after C‐section with general vs. epidural anesthesia: a prospective observational study

“…Although S100β is a highly sensitive biomarker to detect brain damages by various harmful factors 17 , it is relatively less specific as there are S100β. Extra-neural sources of S100β also include muscle, kidney and heart 38,39 . So the specificity of S100β for acute brain injury is generally low 40 .…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…Among the most studied predictors of TBI outcome, age is a consistent predictor, as well as GCS scores and pupillary parameters [18]. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients [19][20][21][22].…”

“…NVU is at the basis of neurovascular coupling, which allows cerebral blood flow to local regulation according to neuronal Traumatic Brain Injury -Pathobiology, Advanced Diagnostics and Acute Managementactivity in specific areas of the brain [34]. TBI may cause mechanical deformation and damage to the entire NVU [20,35,36], compromising barrier integrity and leading to dysautoregulation of brain vessels and BBB disruption. In this context, brain edema may occur and result in increased ICP and decreased cerebral perfusion [37].…”

“…In this context, brain edema may occur and result in increased ICP and decreased cerebral perfusion [37]. In fact, compensatory mechanisms are exceeded as brain volume increases due to edema, and ICP rises exponentially and correlates with increased mortality and poor functional outcomes [20,[38][39][40]. The impact of trauma causes mechanical forces that engender deformation of the brain tissue, resulting in immediate neural damage, called primary injury [40].…”

Improved monitoring dynamics through use of a tethered enzyme biosensor to detect and quantify neuron-specific enolase activity levels in biofluids

“…Cohen et al outcome after cardiac arrest, 7 severe or mild traumatic brain injury (mTBI, concussion 8 ), and Creutzfeldt-Jakob disease. 3 NSE has also been broadly suggested as a diagnostic marker for various kinds of cancers, including small cell lung cancer 9,10 and neuroblastoma, 11 where its concentration correlates with tumor burden, number of metastatic sites, and response to treatment.…”