DIFFERENTIAL MATRIX METALLOPROTEINASE EXPRESSION IN CASES OF MULTIPLE-SCLEROSIS AND STROKE

Multiple sclerosis (MS) and stroke pathology are characterized by bloo d-brain barrier breakdown, leucocyte emigration, and tissue destructio n. Each process is thought to involve the matrix metalloproteinases (M MP), but little is known of their expression. We undertook to investig ate whether MMP expression is dependent on the nature of the CNS lesio n and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A , gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia/macrop hages within acute MS lesions. In active-chronic MS lesions, matrilysi n and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macr ophages within perivascular cuffs. The pattern of MMP expression in in farct lesions differed considerably. Gelatinase-B was strongly express ed by neutrophils in tissue from patients up to 1 week after an infarc t, whereas gelatinase-a and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number o f macrophages present were expressing matrilysin and gelatinase A. Onl y a low level of gelatinase-A and matrilysin expression was observed i n normal brain controls. Thus, MMPs are expressed in inflammatory lesi ons in the CNS, but their individual expression is dependent on the na ture and chronicity of the lesion. However, the general pattern of exp ression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood-brain barrier breakdown and ti ssue destruction, both in MS and in cerebral ischaemia.