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Published on: March 26, 2019
The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes
M-J Hannocks1, X Zhang1, H Gerwien1
1Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
Abstract:
This review focuses on the complementary roles of MMP-2 and MMP-9 in leukocyte migration into the brain in neuroinflammation, studied mainly in a murine model of experimental autoimmune encephalomyelitis (EAE) that has similarity to the human disease multiple sclerosis. We discuss the cellular sources of MMP-2/MMP-9 in EAE, their sites of activity, and how cleavage of the to-date identified MMP-2/MMP-9 substrates at the blood-brain barrier facilitate leukocyte filtration of the central nervous system (CNS). Where necessary, comparisons are made to inflammatory processes in the periphery and to other MMPs relevant to neuroinflammation. While the general principles concerning MMP-2 and MMP-9 function discussed here are relevant to all inflammatory situations, the details regarding substrates and molecular mechanisms of action are likely to be specific for neuroinflammation.
Insights
Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are crucial for guiding immune cells into the brain during neuroinflammation. Understanding their roles in conditions like multiple sclerosis is key.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Pathology
Background:
- Neuroinflammation involves the migration of leukocytes into the central nervous system (CNS).
- Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play a role in inflammatory processes.
- Experimental autoimmune encephalomyelitis (EAE) in mice serves as a model for human multiple sclerosis.
Purpose of the Study:
- To review the complementary roles of MMP-2 and MMP-9 in leukocyte migration into the brain during neuroinflammation.
- To explore the cellular sources and activity sites of MMP-2/MMP-9 in the context of EAE.
- To elucidate how MMP-2/MMP-9 substrates at the blood-brain barrier facilitate CNS leukocyte infiltration.
Main Methods:
- Literature review focusing on studies of MMP-2 and MMP-9 in EAE.
- Analysis of cellular sources and substrate cleavage by MMP-2/MMP-9.
- Comparison with peripheral inflammation and other MMPs.
Main Results:
- MMP-2 and MMP-9 are key mediators of leukocyte entry into the CNS during neuroinflammation.
- Specific substrates cleaved by MMP-2/MMP-9 at the blood-brain barrier are identified as facilitators of leukocyte filtration.
- Cellular sources and activity sites of these MMPs within the EAE model are discussed.
Conclusions:
- MMP-2 and MMP-9 have complementary functions in facilitating leukocyte migration across the blood-brain barrier in neuroinflammation.
- The molecular mechanisms involving MMP-2/MMP-9 substrates are likely specific to neuroinflammatory conditions like multiple sclerosis.
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