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Table of Contents
Vol. 5, No. 3-4, 1998
Issue release date: May–August 1998
Section title: Paper
Neuroimmunomodulation 1998;5:143–159
(DOI:10.1159/000026331)

The Role of Cytokines in the Neuropathology of Stroke and Neurotrauma

Feuerstein G.Z. · Wang X. · Barone F.C.
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa., USA

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 9/4/1998

Number of Print Pages: 17
Number of Figures: 5
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory reaction to a variety of insults including trauma, ischemia, transplantation, viral infections as well as neurodegeneration. Many aspects of this centrally derived inflammatory response parallel to some extent the nature of such a reaction in the periphery. Through the recent application of molecular genetic techniques including PCR, utilization of cDNA probes in conjuncture with the availability of highly specific antibodies, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNFα and IL-1β, is emphasized in the propagation and maintenance of a CNS inflammatory response. This review summarizes evidence in support of a case for ischemia and trauma eliciting an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils early after the onset of brain injury and subsequently monocyte infiltration) and mediators (cytokines, chemokines and adhesion molecules). It is clear that de novo up-regulation of pro-inflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain occurs soon following focal ischemia and trauma and at a time when the tissue injury is evolving. The significance of the inflammatory response and its contribution to brain injury are now becoming better understood. Evidence has emerged in support of the role of cytokines in driving the inflammatory response and that this process is causally related to the degree of brain injury. Evidence reviewed includes: (1) the capacity of specific cytokines to exacerbate brain damage; (2) the capacity of specific cytokine blockade to reduce ischemic brain damage; (3) depletion of circulating neutrophils reduces ischemic brain injury, and (4) antagonists of the endothelial-leukocyte adhesion interactions (e.g. anti-ICAM-1) reduce ischemic brain injury. Targeting the cytokines that drive the brain inflammatory response to injury provides opportunities to intervene with novel therapeutics in stroke and neurotrauma.


  

Author Contacts

Frank C. Barone
Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals
709 Swedeland Road, PO Box 1539
King of Prussia, PA 19406 (USA)
Tel. +1 610 270 6824, Fax +1 610 270 5681, E-Mail Frank_C_Barone@SBPHRD.com

  

Article Information

Number of Print Pages : 17
Number of Figures : 5, Number of Tables : 0, Number of References : 163

  

Publication Details

NeuroImmunoModulation
Official Journal of the International Society for Neuroimmunomodulation

Vol. 5, No. 3-4, Year 1998 (Cover Date: May-August 1998)

Journal Editor: S.M. McCann, Dallas, Tex.; J.M. Lipton, Dallas, Tex.
ISSN: 1021–7401 (print), 1423–0216 (Online)

For additional information: http://www.karger.ch/journals/nim


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 9/4/1998

Number of Print Pages: 17
Number of Figures: 5
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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