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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 |
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Keywords: | traumatic brain injury, chemokine, inflammation, CXCR2, neutrophils |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Neurosciences not elsewhere classified |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Ziebell, JM (Dr Jenna Ziebell) |
ID Code: | 101708 |
Year Published: | 2010 |
Web of Science® Times Cited: | 89 |
Deposited By: | Wicking Dementia Research and Education Centre |
Deposited On: | 2015-07-02 |
Last Modified: | 2016-10-18 |
Downloads: | 0 |
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