title: The rapid decrease in astrocyte-associated dystroglycan expression by focal cerebral ischemia is protease-dependent.
abstract: During focal cerebral ischemia, the detachment of astrocytes from the microvascular basal lamina is not completely explained by known integrin receptor expression changes. Here, the impact of experimental ischemia (oxygen-glucose deprivation (OGD)) on dystroglycan expression by murine endothelial cells and astrocytes grown on vascular matrix laminin, perlecan, or collagen and the impact of middle cerebral artery occlusion on alphabeta-dystroglycan within cerebral microvessels of the nonhuman primate were examined. Dystroglycan was expressed on all cerebral microvessels in cortical gray and white matter, and the striatum. Astrocyte adhesion to basal lamina proteins was managed in part by alpha-dystroglycan, while ischemia significantly reduced expression of dystroglycan both in vivo and in vitro. Furthermore, dystroglycan and integrin alpha6beta4 expressions on astrocyte end-feet decreased in parallel both in vivo and in vitro. The rapid loss of astrocyte dystroglycan during OGD appears protease-dependent, involving an matrix metalloproteinase-like activity. This may explain the rapid detachment of astrocytes from the microvascular basal lamina during ischemic injury, which could contribute to significant changes in microvascular integrity.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Milner
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hung
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Spatz
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: del Zoppo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D049030:Dystroglycans / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D007150:Immunohistochemistry; D039161:Integrin alpha6beta4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D010215:Papio; D010447:Peptide Hydrolases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D039161:Integrin alpha6beta4; D049030:Dystroglycans; D010447:Peptide Hydrolases