CCR3, CCR2A and macrophage inflammatory protein (MIP)-1α, monocyte chemotactic protein-1 (MCP-1) in the mouse hippocampus during and after pilocarpine-induced status epilepticus (PISE)

Abstract

Aims: To investigate protein and gene expressions of chemokine subtypes CCR3, CCR2A and their respective ligands macrophage inflammatory protein 1-alpha (MIP-1α), monocyte chemotactic protein-1 (MCP-1) in the normal mouse central nervous system (CNS) and in the hippocampus at different time points during and after pilocarpine-induced status epilepticus (PISE). Methods: CCR3 and MIP-1α protein expressions were mapped in the mouse CNS. The protein and gene expressions of CCR3 and CCR2A and their respective ligands MIP-1α, MCP-1 in the hippocampus were studies by immunocytochemical and quantitative real-time RT-PCR during and after PISE. Results: CCR3 and MIP-1α gene expression and immunopositive neurones were broadly distributed in the CNS. CCR3 and CCA2A gene and their protein expression were downregulated in the hippocampus at 1 h during PISE. The protein expression of MIP-1α, MCP-1 decreased but gene expression increased at 2 h during PISE. In the hilus of the dentate gyrus, significant reduction of the numbers of CCR3, CCR2A, MCP-1 immunopositive neurones occurred from 1 h during to 2 months after PISE, but the number of MIP-1α neurones reduced from 2 h during to 2 months after PISE. Induced expression of CCR3 at 1 week, CCR2A, MCP-1 or MIP-1α at 1 week and 2 months after PISE was found in reactive astrocytes. MCP-1 was also demonstrated in the blood vessels of the hippocampus at 2 months after PISE. Conclusions: CCR3 and MIP-1α may play important functional roles in the mouse brain. The downregulation of CCR3, CCR2A, MIP-1α and MCP-1 in the hippocampal neurones at the acute stage during and after PISE may weaken the neuroprotective mechanisms. However, induced expression of MCP-1 in hippocampal blood vessel may be related to changes in permeability of the blood-brain barrier during epileptogenesis. © 2009 Blackwell Publishing Ltd.