White Matter Damage is Associated with Matrix Metalloproteinases in Binswanger’s Disease

Abstract

81 BACKGROUND: Binswanger’s disease (BD) is a progressive form of vascular dementia (VaD) of the elderly associated pathologically with demyelination and clinically with disturbances of gait and intellect. It is commonly found in patients with fibrinoid and hyaline changes in brain arterioles secondary to long-standing hypertension. Because of the remodeling seen in the blood vessel wall, and the role of the matrix metalloproteinases (MMPs) in extracellular matrix injury and repair, we hypothesized that disturbances in the MMPs may be involved in the BD type of VaD. METHODS: To test the hypothesis, brain tissues from five patients with VaD of the BD or multi-infarct type were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a macrophage/microglial cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from eight elderly patients: four with strokes without dementia, and four without neurological diseases. RESULTS: Macrophage/microglia (PG-M1)-positive cells appeared around infarcts both in cases with strokes without dementia, and in those with VaD. In two of the three BD patients PG-M1 cells were prominent near damaged arterioles and scattered diffusely in white matter. MMP-2 was seen normally in perivascular macrophages and astrocytic processes near blood vessels, and was present in patients with strokes in reactive astrocytes, particularly those with a gemistocytic shape. MMP-9 was seen only in acute lesions. MMP-3 was seen in PG-M1 staining microglia/macrophage cells around the acute infarctions. In BD MMP-3 persisted in tissue macrophages, disappearing in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs participate in the demyelination associated with injured blood vessels in the BD form of VaD. Chronic inflammation, which may be amenable to treatment, may be a factor in the progressive forms of VaD.