Paediatric Traumatic Brain Injury: The Evolving Role of Blood and Salivary Biomarkers

Author(s): Livia Barenghi, Alberto Barenghi, Matteo Vidali

Traumatic brain injury is an important priority in intensive care, particularly in paediatrics. Many brain biomarkers, particularly serum glial fibrillary acidic protein, S100 calcium-binding protein B and ubiquitin C-terminal hydrolase L1, have been proposed to improve sensitivity and specificity of diagnosis and management. This is particularly important for identifying clinically significant mild traumatic brain injury in paediatric patients, as it could potentially reduce unnecessary hospitalisations and neuroimaging scans. This manuscript focuses on recent clinical guidelines and research on clinical chemistry tests for various biological fluids, particularly saliva. The text discusses biomarkers in adults and children, highlighting their application in blood and saliva, focused on studies published between January 2021 and June 2025. Firstly, we report on the characteristics of brain biomarkers and the relevance of serum biomarkers of mild traumatic brain injury in paediatric population, as well as the its epidemiology in paediatric and adult populations. Then, we focuses on six important areas: a) Diagnostic guidelines and the rationale for biomarkers: a) Neuroanatomical and functional vulnerabilities in paediatric traumatic brain injury; b) Molecular mechanisms of injury and inflammation in paediatric traumatic brain injury; c) Saliva as an emerging matrix for traumatic brain injury biomarkers; e) Analytical, biological and clinical challenges in biomarker use; f) Experimental biomarkers: exosomes and non coding RNAs.

Research and their potential clinical applications is promising. However, many challenges remain in controlling for biological variability and potential pre- and analytical confounding factors in order to obtain reference values and cut-offs, particularly for salivary biomarkers, and to implement them in paediatric clinical practice.