19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide “neuroprotection” in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-α, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.

          Related collections

          Most cited references163

          • Record: found
          • Abstract: found
          • Article: not found

          Mitogen-activated protein kinase pathways.

          Nearly all cell surface receptors utilize one or more of the mitogen-activated protein kinase cascades in their repertoire of signal transduction mechanisms. Recent advances in the study of such cascades include the cloning of genes encoding novel members of the cascades, further definition of the roles of the cascades in responses to extracellular signals, and examination of cross-talk between different cascades.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tumor necrosis factor: a pleiotropic cytokine and therapeutic target.

            Advances in the molecular biology of human diseases indicate that the most striking manifestations of illness may be caused not by exogenous pathogenic or tumor products, but rather by toxic peptides produced by the host itself. Tumor necrosis factor (TNF), a polypeptide cytokine produced during infection, injury, or invasion, has proved pivotal in triggering the lethal effects of septic shock syndrome, cachexia, and other systemic manifestations of disease. Because removing TNF from the diseased host may prevent development of the illness, this factor has recently been the focus of intensive research. This review discusses the biology of this cytokine, with particular emphasis on its potential therapeutic role in septic shock and cachexia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inflammatory mediators and stroke: new opportunities for novel therapeutics.

              Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide "neuroprotection" in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-alpha, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.
                Bookmark

                Author and article information

                Journal
                Journal of Cerebral Blood Flow & Metabolism
                J Cereb Blood Flow Metab
                Ovid Technologies (Wolters Kluwer Health)
                0271-678X
                1559-7016
                August 1999
                August 31 2016
                August 1999
                : 19
                : 8
                : 819-834
                Affiliations
                [1 ]Cardiovascular Sciences, DuPont Pharmaceuticals Company, Wilmington, Delaware, U.S.A.
                Article
                10.1097/00004647-199908000-00001
                10458589
                a7e6f71a-01cf-4c60-a53c-c97d39151690
                © 1999

                http://journals.sagepub.com/page/policies/text-and-data-mining-license


                Comments

                Comment on this article