Related Experiment Videos
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
D C Anthony1, B Ferguson, M K Matyzak
1Department of Pharmacology, University of Oxford, UK.
Abstract:
Multiple sclerosis (MS) and stroke pathology are characterized blood-brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion 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/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood-brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.
Insights
Matrix metalloproteinases (MMPs) are involved in central nervous system (CNS) inflammation. MMP expression in multiple sclerosis (MS) and stroke lesions depends on lesion type and age, indicating a role in blood-brain barrier breakdown and tissue damage.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Multiple sclerosis (MS) and stroke share pathological features like blood-brain barrier (BBB) breakdown, leukocyte infiltration, and tissue damage.
- Matrix metalloproteinases (MMPs) are implicated in these processes, but their specific expression patterns in CNS lesions are not well understood.
Purpose of the Study:
- To investigate the expression of specific MMPs (gelatinase-A, gelatinase-B, matrilysin, stromelysin-1) in MS and cerebral infarct lesions.
- To determine if MMP expression correlates with lesion type, chronicity, and histopathology.
Main Methods:
- Immunohistochemical analysis of MS and cerebral infarct tissues.
- Detection of gelatinase-A, gelatinase-B, matrilysin, and stromelysin-1 expression.
- Comparison of MMP expression in acute, active-chronic, and chronic MS lesions, as well as in early and late-stage infarct lesions.
Main Results:
- In acute MS lesions, gelatinases A and B and matrilysin were upregulated in microglia/macrophages.
- In active-chronic MS lesions, matrilysin and gelatinase-A were prominent at lesion borders.
- In infarct lesions, gelatinase-B was expressed by neutrophils early post-infarct, while matrilysin and gelatinase-A were expressed by macrophages in later stages.
Conclusions:
- MMP expression in CNS inflammatory lesions is dependent on the lesion's nature and chronicity.
- The observed patterns of MMP expression, particularly in perivascular cuffs and active lesions, support their role in mediating BBB breakdown and tissue destruction in both MS and cerebral ischemia.