Hippocampal CA1 pyramidal cells and neurotrophic factors in a rat model of vascular dementia following Xiongma drop pill versus Ginkgo leaf tablets

BACKGROUND: Previous studies have demonstrated the neuroprotective effects of Xiongma drop pill (XMDP) in a mouse model of vascular dementia. Neurotrophic factors play an important role in repair and regeneration of injured neurons.OBJECTIVE: To compare the effects of XMDP and Ginkgo leaf tablets on the appearance and number of hippocampal CA1 pyramidal neurons, as well as neurotrophic factor content in brain tissues, during vascular dementia formation to explore the neuroprotective mechanisms of XMDP.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Pharmacology, College of Pharmacy, Harbin University of Commerce between April 2007 and December 2008.MATERIALS: XMDP was prepared by the College of Pharmacy, Harbin University of Commerce,with each 40 mg pill containing ferulic acid (>0.149 mg) and gastrodin (>0.171 mg). Ginkgo leaf tablets were purchased from Taiyuan Qianyuan Pharmacy, China.METHODS: Healthy, adult, male, Wistar rats were randomly assigned to 6 groups: sham-operation,model, XMDP (high-, middle-, and low- dose), and Ginkgo leaf tablets. The 6 groups were subdivided into two subgroups according to administration days, i.e., 30 and 60 days, with 8 animals in each subgroup. Rats in the model, XMDP, and Ginkgo leaf tablets groups were subjected to permanent bilateral ligation of the common carotid artery to establish a vascular dementia model. At 8 days after model establishment, all groups received intragastric administration once daily of the following: 10 mL/kg normal saline in the sham-operation and model groups; 0.4,0.2, and 0.1 g/kg XMDP in the high-, middle-, and low-dose XMDP groups, respectively; and 50 mg/kg Ginkgo leaf tablets in the Ginkgo leaf tablets group.MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe appearance and to quantify the number of hippocampal CA1 pyramidal neurons. Brain-derived neurotrophic factor and nerve growth factor concentrations in brain tissues were detected by enzyme-linked immunosorbent assay.RESULTS: Following model establishment, hippocampal CA1 neurons exhibited pathological changes. Compared with the sham-operation group, the number of pyramidal neurons significantly decreased (P < 0.05 or P < 0.01), and neurotrophic factor concentration increased in the model rats (P < 0.05 or P < 0.01). XMDP attenuated neuronal injury in a dose-dependent manner: the number of pyramidal neurons and neurotrophic factor concentrations were significantly increased compared with the model group (P< 0.05 or P< 0.01). High- and middle-dose XMDP resulted in equivalent effects to Ginkgo leaf tablets. In addition, neurotrophic factor concentrations in all XMDP groups,after 60 days of administration, were remarkably greater than corresponding concentrations at 30 days (P < 0.05 or P< 0.01).CONCLUSION: Hippocampal CA1 pyramidal cells exhibited pathological injury following establishment of the vascular dementia model. Middle- and high-dose XMDP increased neurotrophic factor expression in the brain of vascular dementia rats, which suggested neuroprotection equivalent to Ginkgo leaf tablets.