Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 hyaline changes in brain arterioles with injury to the white matter. Clinically, BD patients have long-standing hypertension with disturbances of gait and intellect. Because matrix metalloproteinases (MMPs) are important in cerebral infarction, we hypothesized that disturbances in the MMPs may be involved in VAD: METHODS: Brain tissues from 5 patients with VaD of the BD or multi-infarct type (MID) were immunostained with antibodies to glial fibrillary acidic protein (GFAP), a microglial/macrophage cell marker (PG-M1), gelatinase A (MMP-2), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). Control tissues were from 8 elderly patients: 4 with strokes without dementia and 4 without neurological diseases. RESULTS: PG-M1+ cells appeared around infarcts in patients with strokes without dementia and in patients with VAD: In 2 of the 3 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 in astrocytic 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-M1+ microglial/macrophage cells around the acute infarctions. In BD, MMP-3 persisted in tissue macrophages and disappeared in long-standing white matter gliosis. CONCLUSIONS: These observations suggest that MMPs may participate in the damage to the white matter associated with VAD: Microglia/macrophage-induced damage, which is amenable to treatment, may be a factor in the progressive forms of VAD:

Type

Journal article

Journal

Stroke

Publication Date

05/2001

Volume

32

Pages

1162 - 1168

Keywords

Aged, Antigens, Differentiation, Astrocytes, Brain, Cerebral Infarction, Dementia, Vascular, Demyelinating Diseases, Disease Progression, Female, Glial Fibrillary Acidic Protein, Gliosis, Humans, Immunohistochemistry, Macrophages, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 3, Matrix Metalloproteinase 9, Matrix Metalloproteinases, Microglia, Middle Aged, Nerve Fibers, Myelinated