EPIDERMAL GROWTH FACTOR-LIKE PROTEIN 7 (EGFL7) – A NOVEL TARGET FOR NEUROPROTECTION IN EXPERIMENTAL STROKE

Cerebral ischemia induces neuroinflammation driven by blood–brain barrier (BBB) disruption and leukocyte infiltration, contributing to neuronal damage. Epidermal growth factor-like protein 7 (EGFL7), an endothelial-derived cytokine and extracellular matrix component, supports BBB integrity and neuronal stem cell differentiation, suggesting a protective role in cerebral ischemia. Our aim was to unravel the role of EGFL7 in stroke. Experimental stroke was induced in mice by middle cerebral artery occlusion (MCAO). Mice either carried a tamoxifen-inducible, endothelial–specific EGFL7 knockout or received daily EGFL7 injections. We assessed infarct size, neuroinflammation and functional outcome by flow cytometry, longitudinal MRI, and neurological scoring up to 14 days after MCAO. In addition, we analyzed the correlation of EGFL7 concentrations in the cerebrospinal fluid of patients with the severity of stroke. Our findings in experimental stroke demonstrate that the inflammatory activity within the central nervous system depends on the presence of EGFL7, as leukocyte infiltration into the brain increased with endothelial EGFL7 deficiency and decreased with EGFL7 therapy. To this end, we had evidence from a previous study in chronic neuroinflammation that EGFL7 might modify immune infiltration. Still ongoing mechanistic studies dissect the contributing messengers in ischemic conditions. Additionally, EGFL7-treated mice had smaller infarcts and improved functional outcome. Endogenous EGFL7 expression was elevated after stroke both in the murine brain and in the cerebrospinal fluid of patients. In patients, higher EGFL7 levels correlated with smaller infarct volumes and lower NIHSS scores. These findings suggest a pivotal role for EGFL7 in stroke indicating neuroprotective properties.