IMR Press / FBL / Volume 11 / Issue 2 / DOI: 10.2741/1883

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic brain
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1 Department of Fundamental Neuroscience, Geneva University Hospital, Geneva Medical School, 1211 Geneva, Switzerland

Academic Editor: Charles Malemud

Front. Biosci. (Landmark Ed) 2006, 11(2), 1289–1301; https://doi.org/10.2741/1883
Published: 1 May 2006
(This article belongs to the Special Issue Fundamental pathways in osteoarthritis)
Abstract

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of several diseases of the CNS, that share common pathophysiological processes, such as blood-brain barrier (BBB) disruption, oxidative stress, remodeling of the extracellular matrix (ECM) and inflammation. In ischemic brain injury, MMPs are implicated in various stages of the disease. Early after the onset of ischemia, MMPs contribute to the disruption of the BBB leading to vasogenic edema and to the influx of leucocytes into the CNS. The ability of MMPs to digest the basal lamina of capillaries increases the risk of hemorrhagic transformation of the ischemic tissue. During the acute ischemic phase, maintenance of the ECM is essential for neuronal survival. However, ECM degradation and its reconstitution are critical to tissue recovery. MMPs as a key modulator of ECM homeostasis play a role in the cascades leading to neuronal cell death and tissue regeneration. This pleiotropic implication of MMPs in brain injury has open new areas of investigation, which should lead to innovative therapeutic strategies. Yet MMPs may have a detrimental or beneficial role depending on the stage of brain injury. Simple therapeutic strategies based on MMP inhibition have thus little chance to favorably alter prognosis.

Keywords
Extracellular Matrix
ECM
Ischemia
Stroke
Multiple Sclerosis
MS
Blood-Brain Barrier
Matrix Metalloproteinases
MMP
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