Matrix metalloproteinases as therapeutic targets for stroke

• Matrix metalloproteinases are important in injury and recovery.
• Blood–brain barrier disruption is an early MMP-mediated process.
• Angiogenesis is a late event mediated by MMPs.
• Treatments will need to consider the early and late effects.

Matrix metalloproteinases (MMPs) are important in injury and recovery in ischemic injury. They are proteolytic enzymes that degrade all components of the extracellular matrix (ECM). They are secreted in a latent form, protecting the cell from damage, but once activated induce injury prior to rapid inactivation by four tissue inhibitors to metalloproteinases (TIMPs). Normally the constitutive enzymes, MMP-2 and membrane type MMP (MMP-14), are activated in a spatially specific manner and act close to the site of activation, while the inducible enzymes, MMP-3 and MMP-9, become active through the action of free radicals and other enzymes during neuroinflammation. Because of the complex nature of the interactions with tissues during development, injury and repair, the MMPs have multiple roles, participating in the injury process in the early stages and contributing to recovery during the later stages. This dual role complicates the planning of treatment strategies.This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.