GFAP Use in Emergency Medicine—A Narrative Review

Background: Traditional clinical assessments for neurological emergencies, such as the Glasgow Coma Scale, are often subjective and may be confounded by factors like intoxication or sedation. While computed tomography (CT) remains the diagnostic standard, it may lack sensitivity for mild traumatic brain injury (TBI) and pose a risk of radiation exposure. Glial fibrillary acidic protein (GFAP), an intermediate filament protein primarily produced by astrocytes in the central nervous system (CNS), has been shown to be a potential objective marker of neuronal distress, even when macrostructural imaging may appear normal. Aims: This narrative review synthesizes recent evidence on the molecular biology and pathophysiology of GFAP in acute CNS injury. It evaluates GFAP’s clinical applications across major neurological emergencies—including TBI, stroke, and sepsis—while comparing its performance to other major biomarkers and identifying the technological and operational hurdles for routine emergency department (ED) implementation. Evidence Synthesis: Following CNS insult, astrocytes undergo reactive astrogliosis, leading to GFAP upregulation and proteolytic cleavage into breakdown products (GFAP-BDP) that provide a unique signature of structural disruption. GFAP exhibits favorable kinetics in the circulation, with a rise within one hour and a peak at approximately 20 h. In TBI, GFAP is FDA-cleared for CT decision-making and demonstrates superior diagnostic accuracy (AUC 0.88–0.89) within the first 30–60 min of injury. Some studies also support its role in distinguishing intracerebral hemorrhage from ischemic stroke according to distinct temporal release patterns and serve as a potential biological marker of CNS involvement in sepsis-associated encephalopathy; though its use is still investigational and requires further validation. Compared with other biomarkers such as S100B, UCH-L1, NSE, and tau, GFAP offers greater CNS specificity and more reliable signals for identifying structural lesions. Conclusions: GFAP represents a transformation tool for objective risk stratification and decision-making in the ED. However, its transition from a research tool to a standard clinical pillar requires the standardization of assay platforms, established reference materials, and large-scale validation of clinical thresholds.