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Extracellular matrix-degrading metalloproteinases and neuroinflammation in stroke

  • Chapter
Inflammation and Stroke

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Cerebral ischemia initiates a complex cascade of molecular events, culminating in irreversible membrane damage and cell death. Important components of the cascade include the release of glutamate, induction of immediate early genes, and the formation of free radicals and proteases. Lipases attack cell membranes; endonucleases damage DNA, causing apoptosis; and neutral proteases disrupt the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) and serine proteases, including the plasminogen activators (PAs), are two important neutral protease gene families that are involved in the neuroinflammatory response after ischemia. Much is known about the biology of these proteases because of the prominent role that the MMPs and PAs play in cancer and arthritis [1]. Intracerebral injection of activated MMP-2 opens the blood-brain barrier (BBB) [2]. Hemorrhage and ischemia increase gelatinases in the brain [3,4]. Infiltrating cells are a source of MMPs in injury. Immunohistochemistry shows that brain cells also produce MMPs after an ischemic injury. MMPs are formed as proenzymes, and require activation. Plasmin, which activates several of the MMPs, is formed by the conversion of plasminogen to plasmin through the action of tissue-type and urokinase-type PA [5]. Plasminogen activators act synergistically with the MMPs in many pathological processes, including those involving the central nervous system [6]. In stroke the use of recombinant tissue plasminogen activator (rtPA) has been shown to be an effective treatment when given acutely, but its use increases the risk of intracerebral hemorrhage by tenfold [7].

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Author information

Authors and Affiliations

  1. Departments of Neurology, Neurosciences, and Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    Gary A. Rosenberg

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  1. Gary A. Rosenberg
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Editors and Affiliations

  1. Cardiovascular Diseases Research Experimental Station, DuPont Pharmaceuticals Company, Route 141 & Henry Clay Road, Wilmington, DE, 19880, USA

    Giora Z. Feuerstein

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© 2001 Springer Basel AG

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Rosenberg, G.A. (2001). Extracellular matrix-degrading metalloproteinases and neuroinflammation in stroke. In: Feuerstein, G.Z. (eds) Inflammation and Stroke. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8297-2_22

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  • DOI: https://doi.org/10.1007/978-3-0348-8297-2_22

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9508-8

  • Online ISBN: 978-3-0348-8297-2

  • eBook Packages: Springer Book Archive

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