Change Of Neurons' CNTF Expression And Lipid Peroxidation In PSD Rats And Treatment Of Mirzatapine

Post-stroke depression(PSD) is one of the most common complications after cerebral vascular disease, and its major clinical manifestation is out of mode, loss of interest and pleasure and so on, which can have a severe influence on the life of the patients, prolong the rehabilitation time, increase the rate of disability and fatality, and increase the load of both patients and their relatives. So PSD is paid more and more attention, and its pathogenesis isn't known completely.The main treatment of PSD is antidepressive drug.At present, most researchers think that the ccurance of PSD is because of the change in neurobiology and psychology, or the combination of the two aspects of pathogenesis. With the development of neurological psychiatric pharmacology, more researchers think neurological nutrition and lipid peroxidation may play an important part in the process of the PSD. This experiment is designed for the futher research of PSD pathogenesis in these two aspects and the anti-depression mechanism of mirtazapine.As one member of the neuroregulation factors, CNTF is different from neurotrophy factors in molecule structure and biologic activity. CNTF has a large varity of biologic activity, which contributes to maintaining the survival of neuron after stroke, inducing differentiation and nerve regeneration. Hippocampus is one position in which the most CNTF receptor distribute. CNTF may protect the neuron of hippocmpus by acting on ion type tunnel of Glu and Ca 2+ intake of calcium pool, inhibiting the increase of Ca 2+ concentration in cytoplasm which is increased by the Glu. Stress can decrease the expression of CNTF and its mRNA, which makes the protection of hippocampus neuron less. So the decrease of endogenous CNTF may one of the reasons of PSD.The effect of lipid peroxidation may cause the membrance of high lipid change , which change its permeability. Lipid peroxidation in serum can make the protein degenerate, deactive the emzyme, hormone and vatamin, schizolyze lysosome, which make neuron die, and ultimately cause the psychiatry disorder. It has been shown that SOD activity decreases, MDA increases in blood plasm when one suffers depression, which suggests there be a relationship between lipid peroxidation afer a stroke and depression.Objective: In order to set up the post-stroke deperssive rat model. To observe the change of depressive behavior, CNTF in hippocampus, and SOD, GSH-Px, MDA, NO in cerebral cortex and serum.. To observe the treatment of mirtazapine. Furthermore, to probe the anti-depressive mechanism of mirtazapine.Method:(1)The establishment of PSD rats: Middle cerebral artery is occluded by advanced Koizumi's method to set up focal cerebral ischemic rat model. On the basis, further isolated-living condition and moderate unpredictable stress are applied successively to set up PSD rat model. The neurological functional recovery of stroke is asscessed by Longa 5 grades.(2)Weight, Sucroese solution consumption test, open-field test were used to estimate the change of interest, the level of spontaneous motor activities and investigative behavior of PSD rat model. (3)The distribution of CNTF in the hippocampus of rats in different groups were investigated with immuohistochemistry; SOD, GSH-Px, MDA, NO in cerebral cortex and serum were tested; and observed the chang of these item in rats which used mirtazapine.Results: (1) The PSD rat model manifests significant changes: neurological functional impairment, weight loss, the decrease of socrose solution consumption, the droping of open-field behaviors. Compared withnormal control, the decreases were remakable(p<0.05). After 28 days of antidepressant treatment, all the records of the behavior testing significantly ameliorated(p<0.05). (2)The expression of CNTF in hippocampus in PSD rats were significant lower than that in the normal control(p<0.01). While the expression of CNTF in the same region in mirtazapine group were marked higher than that in PSD rats(p<0.01). (3)SOD, GSH-Px in both cerebral cortex and serum decreased, and MDA, NO increased remakably. Compared with the normal control, the difference was remarkable(p<0.01). After the treatment by mirtazapine, SOD, GSH-Px increase and MDA, NO decreased, compared with the PSD grouop, the difference was remarkable(p<0.01).Conlusion: (1) On the basis of focal cerebral ischemic rat model, isolated-living condition and moderate unpredictable stress are applied successively to set up suitable PSD rat model. (2) The expression of CNTF decrease in the hippocampus of PSD rats, which means neuron plasticity in hippocampus decreased. That may be one of the pathogenesis mechanisms of PSD. (3)SOD, GSH-Px decreased, while MDA, NO increased in the cerebral cortex and serum of PSD rats, which means PSD may be related to lipid peroxidation. (4) Mirtazapine can improve the behavior of PSD rats, increase the expression of CNTF in hippocampus and SOD,GSH-Px in cerebral cortex and serum, while detrease MDA, NO in the same region. So it's possible that the increase of neuron plasticity in hippocampus and anti- oxidation may be one of the anti-depressive mechanism of mirtazapine.