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Vol. 31, No. 5, 2009
Issue release date: September 2009
Section title: Review
Free Access
Dev Neurosci 2009;31:378–393
(DOI:10.1159/000232556)

Does Inflammation after Stroke Affect the Developing Brain Differently than Adult Brain?

Vexler Z.S.a · Yenari M.A.a, b
aDepartment of Neurology, University of California, and bSan Francisco Veterans Affairs Medical Center, San Francisco, Calif., USA
email Corresponding Author

Abstract

The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative responses, is the major contributor to ischemic injury in both the immature and adult brain, but there are several areas where these responses diverge. We discuss the contribution of various inflammatory mechanisms to injury and repair after cerebral ischemia in the context of CNS immaturity. In particular, we discuss the role of lower expression of selectins, a more limited leukocyte transmigration, undeveloped complement pathways, a more rapid microglial activation, differences in cytokine and chemokine interplay, and a different threshold to oxidative stress in the immature brain. We also discuss differences in activation of intracellular pathways, especially nuclear factor κB and mitogen-activated protein kinases. Finally, we discuss emerging data on both the supportive and adverse roles of inflammation in plasticity and repair after stroke.

© 2009 S. Karger AG, Basel


  

Key Words

  • Stroke
  • Hypoxia-ischemia
  • Cytokine
  • Chemokine
  • Microglia
  • Neuroprotection
  • Neurogenesis

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Author Contacts

Zinaida S. Vexler, PhD
Department of Neurology, University of California, San Francisco
521 Parnassus Avenue, C215
San Francisco, CA 94143-0663 (USA)
Tel. +1 415 502 2282, Fax +1 415 502 5821, E-Mail Zena.Vexler@ucsf.edu

  

Article Information

Received: December 3, 2008
Accepted after revision: March 3, 2009
Published online: August 11, 2009
Number of Print Pages : 16
Number of Figures : 0, Number of Tables : 0, Number of References : 218

  

Publication Details

Developmental Neuroscience

Vol. 31, No. 5, Year 2009 (Cover Date: September 2009)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

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


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative responses, is the major contributor to ischemic injury in both the immature and adult brain, but there are several areas where these responses diverge. We discuss the contribution of various inflammatory mechanisms to injury and repair after cerebral ischemia in the context of CNS immaturity. In particular, we discuss the role of lower expression of selectins, a more limited leukocyte transmigration, undeveloped complement pathways, a more rapid microglial activation, differences in cytokine and chemokine interplay, and a different threshold to oxidative stress in the immature brain. We also discuss differences in activation of intracellular pathways, especially nuclear factor κB and mitogen-activated protein kinases. Finally, we discuss emerging data on both the supportive and adverse roles of inflammation in plasticity and repair after stroke.

© 2009 S. Karger AG, Basel


  

Author Contacts

Zinaida S. Vexler, PhD
Department of Neurology, University of California, San Francisco
521 Parnassus Avenue, C215
San Francisco, CA 94143-0663 (USA)
Tel. +1 415 502 2282, Fax +1 415 502 5821, E-Mail Zena.Vexler@ucsf.edu

  

Article Information

Received: December 3, 2008
Accepted after revision: March 3, 2009
Published online: August 11, 2009
Number of Print Pages : 16
Number of Figures : 0, Number of Tables : 0, Number of References : 218

  

Publication Details

Developmental Neuroscience

Vol. 31, No. 5, Year 2009 (Cover Date: September 2009)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

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


Article / Publication Details

First-Page Preview
Abstract of Review

Received: 12/3/2008
Accepted: 8/3/2009
Published online: 8/11/2009
Issue release date: September 2009

Number of Print Pages: 16
Number of Figures: 0
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

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


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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