The Potential for Bio-Mediators and Biomarkers in Pediatric Traumatic Brain Injury and Neurocritical Care

Patrick M Kochanek,C Edward Dixon,Alicia K Au,Ericka L Fink,Robert S B Clark,Rachel P Berger,Hülya Bayır,Michael J Bell

doi:10.3389/fneur.2013.00040

Abstract

The use of biomarkers of brain injury in pediatric neurocritical care has been explored for at least 15 years. Two general lines of research on biomarkers in pediatric brain injury have been pursued: (1) studies of “bio-mediators” in cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) to explore the components of the secondary injury cascades in an attempt to identify potential therapeutic targets and (2) studies of the release of structural proteins into the CSF, serum, or urine in order to diagnose, monitor, and/or prognosticate in patients with TBI or other pediatric neurocritical care conditions. Unique age-related differences in brain biology, disease processes, and clinical applications mandate the development and testing of brain injury bio-mediators and biomarkers specifically in pediatric neurocritical care applications. Finally, although much of the early work on biomarkers of brain injury in pediatrics has focused on TBI, new applications are emerging across a wide range of conditions specifically for pediatric neurocritical care including abusive head trauma, cardiopulmonary arrest, septic shock, extracorporeal membrane oxygenation, hydrocephalus, and cardiac surgery. The potential scope of the utility of biomarkers in pediatric neurocritical care is thus also discussed.

Highlights

Serum or cerebrospinal fluid (CSF) biomarkers of brain injury have been suggested as possible diagnostic adjuncts in neurocritical care since the groundbreaking work from the laboratory of Per Vaagenes (Kjekshus et al, 1980; Vaagenes et al, 1980, 1984, 1986, 1987, 1988; Bohmer et al, 1983; Vaagenes, 1986) in experimental and clinical cardiac arrest (CA), anoxic brain injury, stroke, and open heart surgery over 30 years ago
Infants who were victims of abusive head trauma (AHT) had CSF proteomic profiles with reduced levels of acute phase reactants such as haptoglobin and complement components vs. children with traumatic brain injury (TBI) from other causes such as motor vehicle accidents. This could reflect a delay in presentation or represent a consequence of repeated injury often seen in cases of AHT
We reported use of three serum biomarkers neuron specific enolase (NSE), S100β, and myelin basic protein (MBP) as aids in prognostication in pediatric CA and observed outstanding performance based on receiver operator characteristic analysis (Fink et al, 2011)

Summary

INTRODUCTION

Serum or cerebrospinal fluid (CSF) biomarkers of brain injury have been suggested as possible diagnostic adjuncts in neurocritical care since the groundbreaking work from the laboratory of Per Vaagenes (Kjekshus et al, 1980; Vaagenes et al, 1980, 1984, 1986, 1987, 1988; Bohmer et al, 1983; Vaagenes, 1986) in experimental and clinical cardiac arrest (CA), anoxic brain injury, stroke, and open heart surgery over 30 years ago. EARLY STUDIES ON BIO-MEDIATORS AND BIOMARKERS OF BRAIN INJURY IN PEDIATRIC TBI Bell et al (1997b) examined CSF levels of the cytokines interleukin-6 (IL-6) and IL-10 in infants and children after severe TBI (Glasgow coma scale score < 8) and reported marked increases of both vs controls. Increases in the CSF levels of cytochrome c after pediatric TBI and its association with AHT and female gender were confirmed in a study examining biomarkers of apoptosis vs necrosis (Au et al, 2012) These studies suggest that apoptotic neuronal death may represent a therapeutic target in pediatric TBI, in infants.

SERUM BIOMARKERS IN PEDIATRIC TBI AND CARDIOPULMONARY ARREST

CONCLUSIONS