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Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and cortical damage following closed head injury

Citation

Semple, BD and Bye, N and Ziebell, JM and Morganti-Kossmann, MC, Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and cortical damage following closed head injury, Neurobiology of Disease, 40, (2) pp. 394-403. ISSN 0969-9961 (2010) [Refereed Article]

Copyright Statement

Copyright 2010 Elsevier Inc

DOI: doi:10.1016/j.nbd.2010.06.015

Abstract

The contribution of infiltrated neutrophils to secondary damage following traumatic brain injury remains controversial. Chemokines that regulate neutrophil migration by signaling through the CXCR2 receptor are markedly elevated by brain injury and are associated with the propagation of secondary damage. This study thus investigated the function of CXCR2 in posttraumatic inflammation and secondary degeneration by examining Cxcr2-deficient (Cxcr2−/−) mice over 14 days following closed head injury (CHI). We demonstrate a significant attenuation of neutrophil infiltration in Cxcr2−/− mice at 12 hours and 7 days after CHI, despite increased levels of CXC neutrophil-attracting chemokines in the lesioned cortex. This coincides with reduced tissue damage, neuronal loss, and cell death in Cxcr2−/− mice compared to wild-type controls, with heterozygotes showing intermediate responses. In contrast, blood–brain barrier permeability and functional recovery did not appear to be affected by Cxcr2 deletion. This study highlights the deleterious contribution of neutrophils to posttraumatic neurodegeneration and demonstrates the importance of CXC chemokine signaling in this process. Therefore, CXCR2 antagonistic therapeutics currently in development for other inflammatory conditions may also be of benefit in posttraumatic neuroinflammation

Item Details

Item Type:Refereed Article
Keywords:traumatic brain injury, chemokine, inflammation, CXCR2, neutrophils
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Ziebell, JM (Dr Jenna Ziebell)
ID Code:101708
Year Published:2010
Web of Science® Times Cited:52
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2015-07-02
Last Modified:2016-10-18
Downloads:0

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