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Background and Purpose With the aging of the population development, vascular dementia (vascular dementia, VD) to become the second largest cause of dementia etiology. Because the disease has a high morbidity and disability, and long duration and high cost of treatment, the patient's family and society a huge burden, so VD treatments become more and more attention. Memantine hydrochloride is noncompetitive N-methyl-D-aspartate (N-methyl-D-aspartate, NMD A) NMDA receptor antagonists, the present study shows its VD effective, but its improved learning and memory in VD function of the specific mechanism is unclear. CAMP response element binding protein (cAMP responsive element binding protein, CREB) is a eukaryotic transcription factors within the nucleus, is a long-term memory formation of \increased release from mitochondria into the cytosol, will lead to apoptosis. But in the VD rat model, the existence of CREB and cytochrome C changes; whether memantine by affecting the expression of CREB and cytochrome C release and achieve improved learning and memory function, there were no reports. Based on this, this study established rat model of vascular dementia, memantine was observed before and after treatment CREB and the expression of cytochrome C, and to explore the possibility of memantine treatment of VD mechanism. The first part of the method to SD rats as the research object, using a permanent bilateral carotid artery ligation method to prepare VD animals were randomly divided into sham operation group, model group, memantine group; modeling group were given memantine hydrochloride postoperative Memantine .3mg/kg (dissolved in saline) once a day, a total of 8w; sham operation group and model group were given saline orally once a day, a total of 8w. The rats were fed after the application of its Y-shaped maze learning and memory tests. Academic higher, indicating poorer learning ability; memory performance greater, indicating that memory as possible. The second part of the HE staining and Nissl staining was observed in hippocampus of rats pathological changes, using SP immunohistochemical technique was CREB in hippocampus of rats and the expression of cytochrome C, using Qwin550CW image processing and analysis system measured CREB and cytochrome C positive reactive substances average gray value; apoptosis by TUNEL assay, and the number of apoptotic cells statistics, statistical indicators as a percentage. Results 1 Y maze test: minimum academic sham-operated rats, the maximum memory performance; model group, the largest academic performance, minimal memory performance, suggesting that the model group learning and memory decline, compared with the sham group was statistically significant (P <0.01 ); memantine group than in the untreated group learning and memory capacity to improve (P <0.01). 2 HE staining: sham hippocampal CA1 neurons regularly arranged dense, large round nucleus, nucleolus clear; model of hippocampal neurons structural disorder, loosely arranged karyopyknosis, stained; memantine group of neurons arranged in a more tightly round the nucleus, nucleolus clear, only see a small pyknotic degeneration of neurons. 3 Nissl staining: sham neurons clear cell structure intact, covered with dark blue cytoplasm Secheng granular Nissl; model group, cell shrinkage deformation, smaller, colored pale cytoplasm Nissl ; memantine group of neurons clearer, more complete cell structure, more abundant cytoplasm Nissl bodies. 4 SP assay the expression of CREB in hippocampus: CREB expression product brownish yellow, in the cytoplasm and nucleus. Sham group showed a large number of positive cells in the cytoplasm and nucleus were seen a lot of brown particles, deeply stained; while the number of positive cells in model group decreased CREB, coloring lighter; positive cells memantine group than in model group increased, dyed darker. CREB positive reaction products showed that the average gray value: model group was significantly lower than the sham group (P <0.01), while the memantine group than in model group was increased, compared with the model group were significantly different (P <0.01) . 5 SP assay the expression of cytochrome C: cytoplasm with brown particles as positive cells. Sham lightest colored cytoplasm; coloring heaviest model group, showing that a large number of colored cytoplasm positive cells was significantly increased release of cytochrome C; memantine group cytoplasmic staining was weak or moderate intensity staining. Cytochrome C positive reaction product of the average gray value in model group than the sham group (P <0.01), while the memantine group compared with model group (P <0.01). 6 cell apoptosis: sham operation group shows a small amount of apoptotic cells, showing nuclei were stained brown or tan, irregular nuclear shape; model group see a lot of apoptotic cells; memantine group compared with the model group decreased apoptotic cells . The results showed that the percentage of apoptotic cell count, model group, the percentage of apoptotic cells increased compared with the sham group (P <0.01), while the memantine group was significantly lower compared with the model group, a significant difference (P <0.01). Conclusion 1 VD decreased expression of CREB in hippocampus, cytochrome C release from mitochondria to the cytoplasm in the process, may be associated with learning and memory in rats with impaired. 2 memantine hydrochloride may inhibit the NMDA receptor, increasing CREB expression, inhibition of cytochrome C release, to improve learning and memory ability of VD rats.
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