Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke

Abstract

Angiogenesis is a key restorative process following stroke but has also been linked to increased vascular permeability and blood brain barrier (BBB) disruption. Previous pre-clinical approaches primarily focused on the administration of vascular endothelial growth factor (VEGF) to promote vascular repair after stroke. Although shown to improve angiogenesis and functional recovery from stroke, VEGF increased the risk of blood brain barrier disruption and bleedings to such an extent that its clinical use is contraindicated. As an alternative strategy, antibodies against the neurite growth inhibitory factor Nogo-A have recently been shown to enhance vascular regeneration in the ischemic central nervous system (CNS); however, their effect on vascular permeability is unknown. Here, we demonstrate that antibody-mediated Nogo-A neutralization following stroke has strong pro-angiogenic effects but does not increase vascular permeability as opposed to VEGF. Moreover, VEGF-induced vascular permeability was partially prevented when VEGF was co-administered with anti-Nogo-A antibodies. This study may provide a novel therapeutic strategy for vascular repair and maturation in the ischemic brain.