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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Research

Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

Authors: Erik A Johnson, Thuy L Dao, Michelle A Guignet, Claire E Geddes, Andrew I Koemeter-Cox, Robert K Kan

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Exposure to the nerve agent soman (GD) causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE). Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model.

Methods

Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus) following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells). Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines.

Results

We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain.

Conclusions

A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.
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Metadata
Title
Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats
Authors
Erik A Johnson
Thuy L Dao
Michelle A Guignet
Claire E Geddes
Andrew I Koemeter-Cox
Robert K Kan
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-41

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