B14

We hypothesize that marker for BBB-integrity (EGFL7) and neuroaxonal damage (NfL) resolve specific pathophysiologic aspects of Multiple Sclerosis (MS) pathology and that their combination helps to improve monitoring of pathological processes within the CNS and prognostic potential in patients with MS. Therefore we first of all plan to experimentally validate EGFL7 and NfL as markers for BBB-integrity and neuroaxonal damage by taking advantage of human and murine in vitro cultures under different conditions and experimental models of acute (focal inflammatory lesion, relapsing-remitting EAE, stroke) and chronic neuronal injury (chronic EAE models). In a second step we plan to unravel the influence of lesion localization within the CNS and their clearance routes from the CNS to the periphery (by modulating meningeal lymphatics, BBB-drainage and myeloid clearance function), on the peripheral marker levels. In a third step we plan to translate our findings to the patient using prospective multicenter cohorts (NationMS, Nalo-MS, Z02).