Pyrrolidine dithiocarbamate (PDTC) inhibits the overexpression of MCP-1 and attenuates microglial activation in the hippocampus of a pilocarpine-induced status epilepticus rat model.

摘要

The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC) on MCP-1 expression and microglial activation in the hippocampus of a rat model of pilocarpine (PILO)-induced status epilepticus (SE). Moreover, seizure susceptibility, frequency and severity as well as brain damage were analyzed and changes in behavior were recorded. Chemokine MCP-1 expression and microglial activation were detected by immunohistochemistry (IHC). Fluoro-Jade C (FJC) and NeuN staining were used for the evaluation of tissue damage. Our results showed that although SE resulted in the upregulation of MCP-1 and microglial activation in the rat hippocampus 24 h after seizure onset, pretreatment with PDTC significantly inhibited the MCP-1 overexpression and attenuated the microglial activation. These effects were accompanied by neurodegenerative amelioration. To the best of our knowledge, these findings indicated for the first time that the activation of the nuclear factor-κB (NF-κB) pathway may contribute to MCP-1 upregulation and microglial activation in the context of epilepsy. PDTC was also shown to exert anticonvulsant activity and to have a neuroprotective effect on the hippocampal CA1 and CA3 regions, potentially through attenuating microglial activation.