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Updated: Nov 15, 2025

An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke
Published on: March 11, 2018
Blood Biomarkers to Differentiate Ischemic and Hemorrhagic Strokes
Alejandro Bustamante1, Anna Penalba1, Cyrille Orset1
1From the Neurovascular Research Laboratory (A.B., A.P., V.L., A.S., E.P., O.V., J.M.), Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona; Department of Neurology (A.B., M.R.), Hospital Universitari Vall d'Hebrón, Barcelona, Spain; Inserm (C.O., D.V.), Université Caen-Normandie, Inserm UMR-S U1237, Physiopathology and Imaging of Neurological Disorders, GIP Cyceron, Caen, France; Department of Specialities of Internal Medicine (L.A., J.C.S.), Faculty of Medicine, University of Geneva, Switzerland; and Department of Clinical Research (D.V.), Caen Normandie Hospital (CHU Caen), France.
Objective:
To validate a panel of blood biomarkers to differentiate between ischemic stroke (IS) and intracerebral hemorrhage (ICH) in patients with suspected stroke.
Methods:
Patients with suspected stroke admitted within 4.5 hours after onset were enrolled. Blood samples were collected at hospital admission. Glial fibrillary acid protein (GFAP), retinol binding protein 4 (RBP-4), N-terminal proB-type natriuretic peptide (NT-proBNP), and endostatin were measured by immunoassays. Cutoff points were obtained for 100% specificity for IS. A high-sensitivity assay to measure GFAP and rapid point-of-care tests (POCTs) to measure RBP-4 and NT-proBNP were used in subsets of patients. Biomarker panels were evaluated in another cohort of 62 stroke mimics.
Results:
A total of 189 patients (154 IS and 35 ICH) were enrolled. Patients with IS had higher RBP-4, NT-proBNP, and endostatin and lower GFAP levels than patients with ICH. The best biomarker combination for the identification of IS was RBP-4+NT-proBNP, which was able to identify 29.7% of patients with IS with 100% specificity. In the subset of patients for whom GFAP was measured with the high-sensitivity assay, RBP-4, NT-proBNP, and GFAP identified 51.5% of patients with IS with 100% specificity. When stroke mimics were included, specificities were reduced to 98.4 and 96.8%, respectively. POCTs of RBP-4 and NT-proBNP showed results similar results to those of conventional ELISAs.
Conclusions:
A biomarker panel including RBP-4, NT-proBNP, and GFAP provided moderate but potentially useful sensitivity rates at 100% specificity for IS diagnosis. If confirmed in future studies, this strategy might allow prehospital treatment in selected patients.
Classification Of Evidence:
This study provides Class I evidence that a biomarker panel including RBP-4, NT-proBNP, and GFAP distinguishes IS from ICH with moderate accuracy.
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