title: 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Ping-Sung
authors.initials: PS
authors.lastname: Chiu
authors.affiliation: Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: shih@csmu.edu.tw.
authors.forename: Shih-Chan
authors.initials: SC
authors.lastname: Lai
mesh_terms: D017185:Angiostrongylus cantonensis / Q000201:enzymology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008590:Meningoencephalitis / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D017206:Strongylida Infections / Q000469:parasitology
chemical_list: D020780:Matrix Metalloproteinase 9
keywords: Angiostrongylus cantonensis; BBB; Claudin-5; Collagen type IV; Matrix metalloproteinase-9; S100B