Effect of modified Bo-yang-Hwan-o-Tang, a polyherbal medicine on the hippocampal neuronal damage in a rat model of global ischemia.

Abstract

Background:Chronic cerebral hypoperfusion has been well-characterized as a common pathological status contributing to vascular dementia (VD). In this study, the neuroprotective effect of modified Bo-yang-Hwan-O Tang (mBHT), a polyherbal medicine for ischemic stroke, was investigated in a rat model for global ischemia.Materials and Methods:Global ischemia model was prepared in Sprague-Dawley rats by the permanent occlusion of bilateral common carotid arteries (two-vessel occlusion [2VO])-induced chronic cerebral hypoperfusion. mBHT at doses of 250 and 500 mg/kg was orally administrated for 4 weeks once a day, 24 h after 2VO. Histopathological change of the hippocampal region was observed by hematoxylin and eosin, Nissl, and Fluoro-Jade B staining and immunohistochemistry with anti-glial fibrillary acidic protein and anti-neuronal nuclei antibodies. The expression of Bax, Bcl-2, and caspase-3 was investigated in the hippocampus by Western blot. The nuclear factor-kappa B (NF-κB) expression was also analyzed in hippocampal CA1 region using immunofluorescence staining.Results:The administration of mBHT at doses of 250 and 500 mg/kg significantly inhibited chronic cerebral hypoperfusion-induced neuronal damage and astroglial activation in the hippocampal CA1 region in 2VO rats. mBHT increased the NF-κB expression in the CA1 neuronal cells but decreased in activated astrocytes. In addition, mBHT significantly decreased the hippocampal expression of Bax and caspase-3 and increased the Bcl-2 expression in 2VO rats.Conclusions:Our data indicate that mBHT has a neuroprotective property in VD induced by chronic cerebral hypoperfusion through inhibiting the hippocampal neuronal damage and astrogliosis.