| Background and objective:As a serious kind of disease,ischemic cerebral vascular disease endangers mankind's health and results in many consequences including paralysis,cognition functional impairment etc.The cerebral infarction caused by middle cerebral artery occlusion accounts for the most part of cerebral vascular disease.Great attention has been paid to nerve function impairment in past years,but much less attention to vascular cognitive impairment. The number of patients with vascular cognitive impairment increases continuously year by year,the impairment not only makes patients suffer long-term pain and low-quality live, but also results in heavy burden for their families.Therapy with medicine including AChE inhibitor(ACEI) is the main way for vascular cognitive impairment.However,this kind of medicine has more side effects and high cost,so it is difficult for patients to take it widely.Therefore,it is necessary for us to find an effective medicine to treat vascular cognitive impairment.During the past few years,people has concerned the relationship between monoamine neurotransmitter(such as 5-HT) and memory.Recent studies have shown SSRIs,widely used for therapy of depression,not only with no anticholinergic adverse effect but also with effect of improving the cognition function of patients with depression effectively and quickly.But the effect of SSRIs on improving cognitive impaiment poststroke still need further evaluation.In our study,the model of MCAo was made by occluding the MCA with thread according to Longa's method.The MCAo rats were treated with agent of ACHI:Donepezil or agent of SSRIs:Cipramil.The relationship between MCAo and cognitive impairment and the effect of these two different agent on cognition impairment were obserbed in order to explore a new therapy for VCI.Methods:The models of MCAo were made by occluding the MCA with thread according to Longa's method.One hundred and twenty-six SD rats were randomly divided into seven including the sham group(group A),the ischemic 30 min group(group Ba),the ischemia 30 min and treated with Donepezil group(group Ca),the ischemic 30min and treated with Cipramil group(group Da),ischemia 90 min group(group Bb),the ischemia 90 min and treated with Donepezil group(group Cb) and ischemic 90min and treated with Cipramil group(group Db).Intragastric administration of 1.65 mg·kg-1 Donepezil was carried out in group Ca and Cb rats and 6.25 mg·kg-1Citalopram was carried out in group Da and Db rats once a day for 14 days.Sodium Chloride was intragastrically administrated into the group A and group Ba,Bb for the same duration.Behavioral ability of rats in all groups were evaluated by neurological test,brain tissue damage stained with by triphenyl tetrazolium chloride(TTC) was observed.Cognitive function of rats was evaluated with morris-maze test and P300 test on 14 days after MCAo.The changes of monoamine neurotransmitters in hippocampus were surveyed with high performance liquid chromatogram.Immunohistochemistry for ChAT of hippocampal neurons were also observed.Results:1,The average P300 latency of rats of group A is 250.00±12.71ms.The latency in group Ba and the group Bb were significantly longer than that of group A(P＜0.01).No significant difference was observed among group A,group Ca and group Da.The P300 latency in group Bb decreased markedly after treated with Donepezil or Cipramil and the abbreviated amplitude of the latency in group Cb were apparently longer than that in group Db.The latency in group Ba,Ca,Da were respectively significant shorter than those in Group Bb(P＜0.01),Cb(P＜0.05),Db(P＜0.01).2,In the place navigation test,the average escape latency(EL) of group Ba and the group Bb were significantly longer than group A(P＜0.01,P＜0.05).No significant differences was observed among group Ba,group Ca and group Da.The ELof group Cb or Db were both improved obviously as compared with group Bb(P＜0.01).The ELof group Cb apparently improved obviously as compared with group Db(P＜0.05).The indexe in group Bb,Cb or Db were respectively significant longer than those in Group Ba,Ca or Da(P＜0.01).3,In spatial probe test,the ratio of swimming time in platform quadrant(tP/tT) of group Ba and the group Bb were significantly lower than group A(P＜0.05,P＜0.01,).No significant difference was observed among group Ba,group Ca and group Da.The ratio of group Cb or Db were both improved obviously as compared with group Bb(P＜0.01),and group Cb apparently improved obviously as compared with group Db(P＜0.05).The ratio in group Bb,Cb or Db were respectively significant lower than those in Group Ba,Ca or Da (P＜0.01).4,In spatial probe test,the ratio of swimming distance in platform quadrant(dP/dT)of group Ba and the group Bb were significantly lower than group A(P＜0.05,P＜0.01,).No significant difference was observed among groupBa,group Ca and group Da.The ratio of group Cb or Db were both improved obviously as compared with group Bb(P＜0.01), and group Cb apparently improved obviously as compared with group Db(P＜0.05).The ratio in group Bb,Cb or Db were respectively significant lower than those in Group Ba,Ca or Da(P＜0.01).5,The content of norepinephrine(NE),5-HT and DA among the monoamine neurotransmitters in hippocampus of group Ba and group Bb were strikingly lower than those in group A(P＜0.05).Although there is a depressing tendency for the content of NE,5-HT and DA in group Ca,Da as compared with group A,no significant differences among the three groups was detected.The content of those neurotransmitters in group Bb increased markedly after treated with Donepezil or Cipramil and the abbreviated amplitude of thecontent in group Cb were apparently longer than those in group Db(P＜0.05, P＜0.01).The content of those neurotransmitters in group Bb,Cb,Db were respectively significant higher than those in group Ba(P＜0.05),Ca(P＜0.05),Da(P＜0.01).6,With immunohistochemistry for CHAT,ChAT-rich cholinergic neurons in hippocampus of control group had shown obvious pathologic changes as compared with that of sham-operated group.The pathologic changes of group Bb was apparently Severe than group Ba and those ratio of group Cb were remarkably higher than group Db.The number of ChAT-rich cholinergic neurons in hippocampus of rats of group Cb,Db was increased as compared with that of control group after therapy.Conclusions:1,The cognitive function impairment can be induced by MCAo and its degree depends on the length of ischemic duration. 2,The cognitive impairment can be effectively improved by Donepezil and Cipramil by different degree.As to the amelioration of cognitive impairment induced by ischemia 90 min,the Donepezil was significantly more effective than Cipramil and there was no significant differences in degree of the amelioration of cognitive impairment induced by ischemia 30 min between Donepezil and Amelioration.The mechanism of these two durgs may be related to improving the function of hippocampal neuron.
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