Post-ischemic brain damage: Pathophysiology and role of inflammatory mediators

Diana Amantea, Giuseppe Nappi, Giorgio Bernardi, Giacinto Bagetta, Maria T. Corasaniti

Research output: Contribution to journalArticle

Abstract

Neuroinflammatory mediators play a crucial role in the pathophysiology of brain ischemia, exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair. Within hours after the ischemic insult, increased levels of cytokines and chemokines enhance the expression of adhesion molecules on cerebral endothelial cells, facilitating the adhesion and transendothelial migration of circulating neutrophils and monocytes. These cells may accumulate in the capillaries, further impairing cerebral blood flow, or extravasate into the brain parenchyma. Infiltrating leukocytes, as well as resident brain cells, including neurons and glia, may release pro-inflammatory mediators, such as cytokines, chemokines and oxygen/nitrogen free radicals that contribute to the evolution of tissue damage. Moreover, recent studies have highlighted the involvement of matrix metalloproteinases in the propagation and regulation of neuroinflammatory responses to ischemic brain injury. These enzymes cleave protein components of the extracellular matrix such as collagen, proteoglycan and laminin, but also process a number of cell-surface and soluble proteins, including receptors and cytokines such as interleukin-1β. The present work reviewed the role of neuroinflammatory mediators in the pathophysiology of ischemic brain damage and their potential exploitation as drug targets for the treatment of cerebral ischemia.

Original languageEnglish
Pages (from-to)13-26
Number of pages14
JournalFEBS Journal
Volume276
Issue number1
DOIs
Publication statusPublished - Jan 2009

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Keywords

  • Brain ischemia
  • Cytokines
  • Matrix metalloproteinases
  • Microglia
  • Neuroinflammation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Amantea, D., Nappi, G., Bernardi, G., Bagetta, G., & Corasaniti, M. T. (2009). Post-ischemic brain damage: Pathophysiology and role of inflammatory mediators. FEBS Journal, 276(1), 13-26. https://doi.org/10.1111/j.1742-4658.2008.06766.x