Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus

Maira L Foresti,Khurshed Katki,Andres Montañez,Russell M Sanchez,Lee A Shapiro,Gabriel M Arisi

doi:10.1186/1742-2094-6-40

Abstract

BackgroundNeuroinflammation occurs after seizures and is implicated in epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. In this work CCR2 and CCL2 expression were examined following status epilepticus (SE) induced by pilocarpine injection.MethodsSE was induced by pilocarpine injection. Control rats were injected with saline instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial cells was examined using imunohistochemical analyses. The number of CCR2 positive cells was determined using stereology probes in the hippocampus. CCL2 expression in the hippocampus was examined by molecular assay.ResultsIncreased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE.ConclusionThe data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures.

Highlights

Neuroinflammation occurs after seizures and is implicated in epileptogenesis
Increased content/6/1/40 motif receptor 2 (CCR2) and C-C motif ligand 2 (CCL2) in the hippocampus after status epilepticus (SE) In normal adult rats, the CCR2 immunohistochemical analysis revealed a sparse distribution of cells expressing CCR2 in the hippocampus
In rats that experienced SE, still sparse, there were significantly more cells labeled with CCR2 (Figure 1)

Summary

Introduction

CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. Chemokine C-C motif ligand 2 (CCL2) is a potent attractant protein for monocytes, being previously denominated monocyte chemoattractant protein-1 (MCP-1). The biological effects of CCL2 are mediated via interactions with its receptor, chemokine C-C (page number not for citation purposes). Journal of Neuroinflammation 2009, 6:40 http://www.jneuroinflammation.com/content/6/1/40 motif receptor 2 (CCR2). Upon binding to CCR2, CCL2 regulates the migration and infiltration of monocytes, T-lymphocytes and natural killer cells to regions of inflammation [1,2,3]. Studies using CCL2 and CCR2 knockout mice have shown that this ligand-receptor complex is involved in mononuclear cell infiltration at sites of inflammation [4,5,6,7]

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Discussion

Conclusion