PMID- 20621186
OWN - NLM
STAT- MEDLINE
DCOM- 20110112
LR  - 20100913
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 40
IP  - 2
DP  - 2010 Nov
TI  - Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and 
      cortical damage following closed head injury.
PG  - 394-403
LID - 10.1016/j.nbd.2010.06.015 [doi]
AB  - 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.
CI  - Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.
FAU - Semple, Bridgette D
AU  - Semple BD
AD  - National Trauma Research Institute, The Alfred Hospital, Melbourne, Victoria, 
      Australia. Bridgette.Semple@monash.edu
FAU - Bye, Nicole
AU  - Bye N
FAU - Ziebell, Jenna M
AU  - Ziebell JM
FAU - Morganti-Kossmann, M Cristina
AU  - Morganti-Kossmann MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100716
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Interleukin-8B)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Blood-Brain Barrier/pathology
MH  - Cell Death
MH  - Cerebral Cortex/*immunology/pathology
MH  - Chemokines/immunology
MH  - Cytokines/immunology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Head Injuries, Closed/*immunology/pathology
MH  - Heterozygote
MH  - Homozygote
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Neutrophil Infiltration/*immunology
MH  - Receptors, Interleukin-8B/*deficiency/genetics
MH  - Recovery of Function
EDAT- 2010/07/14 06:00
MHDA- 2011/01/13 06:00
CRDT- 2010/07/13 06:00
PHST- 2010/04/13 00:00 [received]
PHST- 2010/06/23 00:00 [revised]
PHST- 2010/06/26 00:00 [accepted]
PHST- 2010/07/13 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2011/01/13 06:00 [medline]
AID - S0969-9961(10)00211-1 [pii]
AID - 10.1016/j.nbd.2010.06.015 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2010 Nov;40(2):394-403. doi: 10.1016/j.nbd.2010.06.015. Epub 2010 
      Jul 16.