Molecular imaging of the inflamed blood-brain barrier: Characterization of the fibrin-fibronectin mesh in acute and chronic inflammation

• Applicant: Dr. Johannes Lohmeier
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546474845

Disruption of the blood-brain barrier (BBB) is an early pathophysiological event observed in the onset of multiple sclerosis (MS), present prior to lesion formation and evident also in normal-appearing white and grey matter. Barrier permeability is characteristically an order of magnitude higher in acute lesions compared to chronic inflammation. The requirements for the signal-to-noise ratio for investigating BBB dysfunction in chronic inflammation is higher due to a lower degree of barrier dysfunction. Clinically-used imaging methods show limited value for the investigation of chronic inflammation and treatment response. Following CNS injury, the extracellular matrix (ECM) is extensively remodeled, including fibrin and fibronectin deposition, and its composition is a major determinant of disease outcome. While conventional and/or advanced MRI is restricted in capturing ECM remodeling, molecular neuroimaging can non-invasively determine neuromolecular signatures in vivo with high sensitivity and specificity. Here, we focus on two distinct proinflammatory mediators within the ECM, fibrin and fibronectin, which are only deposited in the disease state and interact by forming a stable mesh. Neuromolecular signatures in MS may facilitate detection and/or prediction of chronic (smouldering) disease progression, thereby leading to a better understanding of the inflammatory component of MS pathophysiology, while improving therapy assessment by using novel ECM-derived biomarkers. Therefore, the objective is to investigate the role of fibrin and fibronectin as potential imaging biomarkers for acute and chronic inflammation, therapy assessment and remyelination using a pre-clinical murine model of multiple sclerosis.

• DFG Programme: Research Grants