Investigation of circulating biomarkers in combination with computer tomography (CT) and magnetic resonance imaging (MRI) markers to improve diagnosis of ischaemic stroke

Background: The current diagnosis of stroke remains largely clinical but widely used stroke scoring systems do not allow differentiation between stroke patients and mimics (e.g., migraine, seizures). Computed tomography (CT) can confirm haemorrhage, but many patients with suspected stroke are subsequently found to have alternative pathologies. Magnetic resonance imaging (MRI) distinguishes between acute strokes and mimics, but the majority of patients do not tolerate longer scanning time. Recently, the blood biomarker strategy showed a promising diagnostic method, however, there are limited studies examining circulating biomarkers in acute stroke patients compared to mimics as defined by both neurological scores and imaging data. Hypothesis: The combination of circulating biomarkers in acute stroke patients with neurological scores, CT and MRI data can improve the diagnosis of stroke. Methods: Two murine stroke models were used to examine cellular and blood brain barrier (BBB) tight junctional (TJ) markers in the brain by immunohistochemistry and western blotting and assess circulatory biomarkers by ELISA. The serum biomarker levels were measured in stroke patients and mimics identified by both neurological scores and imaging data. Results: Neuronal, glial cell and BBB damage in the brain and changes in circulatory biomarkers were observed in stroke mice compared to shams. The clinical study showed the levels of glial fibrillary acidic protein (GFAP), Neurofilament light chain (NfL) and TJ proteins can differentiate between strokes and mimics. GFAP level is correlated with CT data and Neuron-specific enolase level is correlated with MRI data. Conclusion: The preclinical studies for the first-time demonstrated brain damage together with changes in circulatory markers in two murine models of stroke. The novel clinical study confirmed the preclinical results and suggested that biomarkers in combination with stroke scales and imaging might offer valuable tools for differentiation between ischaemic stroke and mimics and assessing the severity of ischaemic stroke.