Matrix metalloproteinase-9 leads to blood–brain barrier leakage in mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

Abstract

Blood–brain barrier (BBB) disruption is associated with tight junction protein degradation, basal membrane disruption, and astrocyte damage. This study aims to investigate the role of matrix metalloproteinase (MMP)-9 in BBB disruption during Angiostrongylus cantonensis infection. We used mice infected with A. cantonensis, in which parasite-induced eosinophilia and inflammation might induce MMP-9 elevation. MMP-9 could cause claudin-5 degradation in endothelium tight junction, collagen type IV degradation in basal membranes, and S100B degradation in astrocytes of wild-type mice. BBB permeability was significantly attenuated in MMP-9 knockout mice than in wild-type mice in angiostrongyliasis meningoencephalitis. Immune cell aggregates were also more attenuated in the brains of MMP-9 knockout mice than in the brains of wild-type mice. Results suggest that MMP-9 activities are significant in BBB disruption in angiostrongyliasis meningoencephalitis. This study improves understanding of molecular mechanisms that underlie brain invasion by A. cantonensis, which is a key step in the pathogenesis of meningoencephalitis, and can offer a new strategy to reduce mortality.