White matter damage is associated with matrix metalloproteinases in vascular dementia

Background and Purpose-Vascular disease causes multi-infarct dementia (MID) or Binswanger's disease (BD), the latter of which is a progressive form of vascular dementia (VaD) associated pathologically with fibrinoid and hyali ne changes in brain arterioles with injury to the white matter. Clinically, ED patients have long-standing hypertension with disturbances of gait and intellect. Because matrix metalloproteinases (MMPs) are important in cerebr al infarction, we hypothesized that disturbances in the MMPs may be involve d in VaD. Methods-Brain tissues from 5 patients with VaD of the ED or multi-infarct t ype (MID) were immunostained with antibodies to glial fibrillary acidic pro tein (GFAP), a microglial/macrophage cell marker (PG-MI), gelatinase A (MMP -2), stromelysin-l (MMP-3), and gelatinase B (MMP-9). Control tissues were from 8 elderly patients: 4 with strokes without dementia and 4 without neur ological diseases. Results-PG-M1+ cells appeared around infarct in patients with strokes witho ut dementia and in patients with VaD. In 2 of the 3 ED patients, PC-Mi cell s were prominent near damaged arterioles and scattered diffusely in white m atter. MMP-2 was seen normally in perivascular macrophages and in astrocyti c processes near blood vessels and was present in patients with strokes in reactive astrocytes. MMP-9 was rarely seen. MMP-3 was seen in PG-MIS microg lial/macrophage cells around the acute infarctions. In ED, MMP-3 persisted in tissue macrophages and disappeared in long-standing white matter gliosis . Conclusions-These observations suggest that MMPs may participate in the dam age to the white matter associated with VaD. Microglia/macrophage-induced d amage, which is amenable to treatment, may be a factor in the progressive f orms of VaD.