Preventive Effects Of Naloxone On Spatial Learning And Memory Impairment In Rats With Vascular Dementia And The Research Of Neurological Mechanisms

Background and Objective: With of ageing society is coming, dementia has become a frequent-occurring disease, in which vascular dementia (VD) takes the second place. The clinical manifestations of VD include intelligence impairment such as learning and memory deficits and aggravation progressively; ultimately absolute intelligence decline. The cognitive impairment of VD is caused by special vascular mechanism and may be the unique disease which can be prevented in the dementia. Cerebral ischemia causes a series of endogenous opioid peptides(EOP) changes , including B -endorphine's rising . EOP exert many effects through interaction with other transmitters. Hippocampal CA1 region is specially vulnerable to cerebral ischemia, which selectively damages neurons in CA1 field. Hippocampal injury can cause spatial learning and memory disorders.Naloxone , a universal opioid receptor antagonist, acts on many opioid receptors and has wide-ranging pharmacological actions. It can prevent B -endorphines rising and contribute to the modulation of cholinergic system and suppress choline acetyltransferase(ChAT) decreasing after cerebral ischemia . It can stabilize cellular membrane and attenuate calcium influx . Taken together, all of these actions suggest it may protect the neurons in CA1 region fromdamage induced by cerebral ischemia.Thus, the purpose of our current study is to explore the effects of cerbral ischemia ,as well as treatment with naloxone, on spatial learning and memory, ultrastructural changes in hippocampal CA1 region, intracellular calcium of pyramidal cells and ChAT activity in CA1 field of rats with VD.Materials and Methods: 18 -month old Sprague-Dawley(SD) rats were randomly divided into model group, preventive therapeutic group and sham-operated group, each group has ten rats respectively. Model and preventive therapeutic groups were made permanent occlusion of the bilateral carotid arteries, sham-operated group was treated with the same as other two groups except permanent occlusion of bilateral carotid arteries. The preventive therapeutic group was intraperioneally injected naloxone(0.8mg/kg) after the operation immediately , while sham-operated group and model group were intraperioneally injected eaqual volume of saline for 7 days successively. Morris water maze(MWM) trainings were used to observe hidden visible platform escape latency and spatial probe test . Nissl and HE staining were adopted to count the number of pyramidal cells and observe the changes of histopathology in hippocampal CA1 region, respectively. Routine transmission electron-microscope was used to observed ultrastructural changes of CA1 region. Laser scanning confocal microscope was used to measure intracellular calcium fluorescence pixel values of hippocampal neurons. Immunohistochemistry and computerized technique were applied to quantitatively analyze the expression levels of ChAT activity in hippocampal CA1 region's pyramidal cells.Results: Hidden platform escape latency of MWM in modelgroup(21.26s±17.41s) is significantly longer than that in sham-operated group(7.80s±4.70 s) and preventive therapeutic group(8.10s±2.93 s)(P<0.01); the results of the probe test model group(4.44±1.74 times/s) is less than that in sham-operated(8.45±1.19 times/s) and preventive groups(8.00±1.17 times/s)(P<0.01). There are no significantly differences of above two indexes between sham-operated and preventive groups (P>0.05). There have no significantly differences in visible platform escape latency among the three groups. Together the above statistical data, all of the rats in model group meet the criterion on dementia.The quantity of pyramidal cells in hippocampal CA1 region inmodel group ( 43.68±17.29 ) is significantly less than that insham-operated (124.51±14.18) and preventive groups (113.36±13.15)(P<0.01) ; there was no significantly difference between the lattertwo groups(P>0.05).With HE staining, the CA1 pyramidal cells layers of model group were arranged sparse,almost disapp...