Neuroprotective and behavioural assessments of an imidazolium compound (DBZIM) in a rat model of Parkinson's disease induced by 6-OHDA

摘要

The neuroprotective effect of DBZIM, a novel imidazolium compound, has previously been documented to slow down neurodegeneration in a mouse model of Parkinson's disease. In this study, we conducted behavioural studies and further investigated the neuroprotection in a rat Parkinsonian model induced by 6-hydroxydopamine (6-OHDA). DBZIM was found to significantly reduce the 6-OHDA-induced asymmetrical rotation and preferential usage of contralateral forelimbs. Furthermore, the degeneration of tyrosine hydroxylase immunopositive (TH+) dopaminergic neurones in the substantia nigra par compacta (SNc) was illustrated by immunohistochemistry. The significant loss of TH+ neurones by 6-OHDA administration was ameliorated by three different closes of DBZIM treatment in a bell-shape manner. Such neuroprotection was also observed in the 6-OHDA-lesioned striata. High-performance liquid chromatography (HPLC) analysis of the striatal tissues revealed that DBZIM beneficially maintained the dopamine level by slowing down its metabolism. In addition, DBZIM attenuated the activation of astrocytes and microglia. This suggests that anti-inflammation may be an additional mechanism underlying the DBZIM-mediated neuroprotection. These findings warrant further investigation of DBZIM as a promising and potent agent for the future treatment of Parkinson's disease. (C) 2013 Elsevier B.V. All rights reserved.