ABSTRACT
Objective To probe the neuroprotective effect of memantine in hippocampal CA1 region of rats with vascular dementia(VD). Methods 36 male Wistar rats were randomly divided into sham-operated group,VD group and memantine group,and each group have 12 rats. Rats of VD were treated with a permanent bilateral common carotid arteries occlusion(2-VO). Then memantine was given by intragastric administration.The behavioral abnormalities were investigated by Y-type maze test.The changes of cell morphology and the expressions of neuronal nitric oxide synthase(nNOS) and cysteine proteinase-3 (Caspase-3) of neuron in hippocampal CA1 region were detected by HE stain and immunohistochemistry respectively.The percentage of neuronal apoptosis by TUNEL. Results Compared with VD group and sham-operated group,the performance records of learning and memory(learning records:63.16±1.75,79.25±2.01,50.83±1.80,F =707.91,P <0.01;memory records:53.17±1.85,69.17±1.70,40.67±1.83,F =762.43,P <0.01),the expressions of nNOS (average gray scale:140.23±2.30,175.87±3.34,105.63±3.52,F =1539.67,P <0.01)and Caspase-3 (average gray scale:132.78±5.36,162.78±5.25,99.54±5.06,F =439.37,P <0.01)and the percentage of neuronal apoptosis (33.75±2.70,56.17±3.56,6.33±3.65,F =672.91,P <0.01)of memantine group were in the middle. Conclusion Memantine can improve spatial memory and attenuate neuronal apoptosis by down-regulation excessive expression of nNOS and Caspase-3 in rats with vascular dementia.
ABSTRACT
Objective To investigate the effects of memantine hydrochloride on the learning and memory function in vascular dementia (VaD) in rats and its possible mechanism.Methods A rat VaD model was induced by using permanent bilateral common carotid artery ligatioa A total of 36 SD rats were randomly divided into sham-operation group, VaD group,and memantine group (memantine hydrochloride was given by intragastric administration, once a day, for eight weeks) (n = 12 in each group). Y maze test was used to observe their behavioral changes. Immunohistochemistry technique was used to detect the changes of the expressions of cAMP responsive element binding protein (CREB) and cytochrome c (CytC) in hippocampal CA1 region and cortex; and TUNEL method was used to detect neuronal apoptosis. Results The learning and memory abilities in memantine group were 50.17 ± 5.56 and 7.08 ± 0.90 respectively, and they were significantly better than 66.36 ± 5.41 and 4.64 ± 1.03 in the VaD group (all P＜0.01); the mean absorbencies of CREB in hippocampal CA1 region and cortex were 147.51 ± 7.11 and 155.37 ± 4.52, respectively, and they were significantly higher than 135.11 ± 8.52 and 142.39 ± 5.24 in the VaD group (all P＜0.01); and the mean absorbencies of CytC in hippocampal CA1 region and cortex were 116.53 ± 4.91 and 113.51 ± 6.05, and they wre significantly lower than 136.65 ±7.43 and 138.09 ±4.88 in the VaD group (all P ＜ 0.01); the extent of apoptosis in the memantine group was also improved significantly compared to the VaD group. Conclusions Memantine hydrochloride may improve the learning and memory function in VaD rats by upregulating the expression of CREB and inhibiting the release of CytC and neuronal apoptosis.
ABSTRACT
Excitatory amino acid toxicity is one of the mechanisms of vascular dementia. Gluta-mate is the major excitatory neurotransmitter in brain. Memantine, a moderate affinity, uncom-petitive and voltage-dependent N-methyl-D-aspartate (NMDA) receptor blocker, can block NMDA receptor-induced intracellular calcium overload and prevent excitotoxicity. It can be used in the treatment of vascular dementia.
ABSTRACT
Objective To probe the neuroprotective mechanism of Donepezil in hippocampus of mice with vascular dementia(VD).Methods The mice were subjected for reperfusion repeatedly on bio-lateral common carotid arteries by repeatedly clipping and injected sodium nitroprusside into the abdominal cavity to establish the imitative VD rat models.Then Donepezil was given by intragastric administration.The behavioral abnormalities were investigated by Y-type maze test.The expressions of N-methy1-D-aspartate receptor subunit proteins(NR1)in neuron of hippocampus were observed by immunohistochemistry technique,and the activities of glutathione peroxidase(GSH-PX)and catalase(CAT)were measured with dithio-bis-nitrobenzoic acid(DTNB)and ultraviolet spectrophotometry(UV)methods,respectively.Results Compared with VD control group,the performance records of learning and memory in Donepezil group were better(all P