Astroglial Proteins as Diagnostic Markers of Acute Intracerebral Hemorrhage—Pathophysiological Background and Clinical Findings

Abstract

The time span from symptom onset to treatment initiation remains a critical variable determining the efficacy of thrombolysis in acute ischemic stroke. To date, performing a brain scan is indispensable prior to therapy in order to differentiate between patients with ischemic stroke and those with intracerebral hemorrhage (ICH). This causes substantial treatment delay, as thrombolysis cannot be applied prior to hospital admission at much earlier time points. Recently, brain-specific astroglial proteins (i.e., glial fibrillary acidic protein (GFAP), S100B) were identified to be released rapidly from the cytoplasm of destroyed cells in case of acute ICH. Elevated serum concentrations were found within the first 6 h after ICH onset. In contrast, in ischemic stroke, these proteins are released with delay, mirroring the more gradual occurrence of necrotic cell death and blood brain barrier disruption. S100B and GFAP may qualify as candidate serum biomarkers which are able to differentiate between ischemic stroke and ICH in the emergency phase of stroke. This minireview enlightens the pathophysiological background of this finding and provides an overview on currently available clinical data.

Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein for Differentiating Intracerebral Hemorrhage and Cerebral Ischemia in Patients with Symptoms of Acute Stroke

“…In contrast, in ischemic stroke, the structural integrity of brain cells and the blood-brain barrier are preserved for a longer time after symptom onset. Necrotic cell death and cell lysis typically do not occur within the first 6 -12 h after vessel occlusion (17,18 ). This histopathological observation correlates well with the finding that astroglial proteins (S100B, GFAP) are released into plasma with delay, not reaching peak concentrations before 48 -72 h after ischemic stroke onset (23)(24)(25)(26).…”

“…blood of healthy individuals (13 ), but it is released rapidly into plasma in the presence of an expanding intracerebral bleed, owing to the instantaneous destruction of astrocytes and the blood-brain barrier (14,15,17 ). In contrast, in ischemic stroke, the structural integrity of brain cells and the blood-brain barrier are preserved for a longer time after symptom onset.…”

“…As discussed above, the release of GFAP into plasma reflects astroglial cell death with loss of cellular integrity and cell lysis. However, the number of cells that will die has not yet been determined in the very early phase of ischemic stroke (17 ). It is known that a transient perfusion deficit alone leading to functional but not structural damage on the cellular level does not cause GFAP release into the bloodstream (26 ).…”

“…Explorative studies have shown that GFAP is released rapidly in acute ICH, whereas a more delayed release can be observed in patients with ischemic stroke (14 -16 ). This delayed release reflects the more gradual occurrence of necrosis and cytolysis found histopathologically in ischemic stroke, in contrast to the immediate cell destruction in case of ICH (17,18 ). GFAP may therefore function as a biomarker indicating ICH in patients with symptoms suspicious for acute stroke.…”

Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

“…This detrimental process is associated with release of different cell-type specific proteins including calcium-binding protein S100B, glial fibrillary astrocytic protein (GFAP) and neurofilaments (Nf) into extracellular fluids (ECF). From the ECF, these proteins diffuse to the CSF and peripheral blood, where they can be quantified [2]. Increased attention has been directed to establishing the measurement of these molecules as a tool to assist in diagnosis, selection of treatments, assessment of the efficacy of treatments, and prediction of outcome of stroke [3].…”