Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 35, Issue 5, Pages 496-514Publisher
WILEY
DOI: 10.1111/j.1365-2990.2009.01022.x
Keywords
chemokine receptors; ligands; hippocampus; status epilpticus epilepsy
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Funding
- NMRC [NMRC/0960/2005, NMRC/0670/2002, NMRC/0731/2003]
- Singhealth foundation [SHF/FG217P/2005, SHF/FG382P/2007]
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Aims: To investigate protein and gene expressions of chemokine subtypes CCR3, CCR2A and their respective ligands macrophage inflammatory protein 1-alpha (MIP-1 alpha), 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-1 alpha protein expressions were mapped in the mouse CNS. The protein and gene expressions of CCR3 and CCR2A and their respective ligands MIP-1 alpha, MCP-1 in the hippocampus were studies by immunocytochemical and quantitative real-time RT-PCR during and after PISE. Results: CCR3 and MIP-1 alpha 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-1 alpha, 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-1 alpha neurones reduced from 2 h during to 2 months after PISE. Induced expression of CCR3 at 1 week, CCR2A, MCP-1 or MIP-1 alpha 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-1 alpha may play important functional roles in the mouse brain. The downregulation of CCR3, CCR2A, MIP-1 alpha 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.
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