title: Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke.
abstract: Matrix metalloproteinases (MMPs) are a family of more than twenty secreted and cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in blood-brain barrier injury and neuronal death after cerebral ischaemia. On the other hand, very little is known about the expression of the other secreted MMPs. Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and subacute (72 h) stages following transient focal cerebral ischaemia and treatment with recombinant tissue plasminogen activator (rtPA). We observed a significant increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute stage of reperfusion, which was further amplified during the subacute stage for MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and TIMP2 was observed. However, rtPA treatment induced a rapid increase in MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute stage of reperfusion compared to saline treatment, which may have potential implications in the early disruption of the blood-brain barrier after rtPA treatment.
authors.forename: S
authors.initials: S
authors.lastname: Lenglet
authors.forename: F
authors.initials: F
authors.lastname: Montecucco
authors.forename: F
authors.initials: F
authors.lastname: Mach
authors.forename: K
authors.initials: K
authors.lastname: Schaller
authors.forename: Y
authors.initials: Y
authors.lastname: Gasche
authors.affiliation: Jean-Christophe Copin, Division of Cardiology, Fondation for Medical Researches, Avenue de la Roseraie 64, 1205 Geneva, Switzerland, E-mail: jean-christophe.copin@unige.ch; Jean_Copin@yahoo.com.
authors.forename: J-C
authors.initials: JC
authors.lastname: Copin
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism*; D057507:Mice, 129 Strain; D012333:RNA, Messenger / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D015912:Thrombolytic Therapy; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D005343:Fibrinolytic Agents; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D010959:Tissue Plasminogen Activator; D053505:Matrix Metalloproteinases, Secreted
keywords: Brain ischaemia; MMP; TIMP; animal model; tPA