Early screening for post-stroke depression and its effect on functional outcomes, quality of life, and mortality: A meta-analysis

BACKGROUND Post-stroke depression(PSD)is a common and debilitating condition affecting stroke survivors,significantly impacting their recovery and overall quality of life.AIM To assess the effects of early PSD screening on functional outcomes,quality of life,and mortality.METHODS From an initial pool of 1065 articles,6 studies met the inclusion criteria and were selected for analysis.Functional outcomes were measured using the functional independence measure(FIM).RESULTS The analysis revealed a significant improvement in FIM scores for a PSD scree-ning group compared to controls[standardized mean difference(SMD)=8.90,95%confidence interval(CI):4.65-13.15,P<0.01].Quality of life was assessed using the Stroke-Specific Quality of Life Scale,with the screening group showing significantly higher scores(SMD=20.83,95%CI:15.27-26.38,P<0.01).Mortality analysis indicated a reduction in five-year mortality rates for the PSD screening group.CONCLUSION Early PSD screening enhances functional recovery,improves quality of life,and reduces mortality rates in stroke survivors.Thus,integrating PSD screening into routine stroke care improves long-term outcomes for patients.

Clinical Study of Acupuncture Combined with Emotional Intervention in Patients with Post-Stroke Depression

Objective:To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression(PSD).Methods:A total of 100 patients with PSD who met the inclusion criteria were randomly divided into an experimental group(50 cases)and a control group(50 cases)using the random number table method,and the enrollment was in order of admission time.The control group used conventional treatment of oral antidepressant Deanxit tablets(0.5 mg flupenthixol+10 mg melitracen)with the dose appropriately adjusted according to the patient’s medication effect,and modern rehabilitation treatment given selectively according to the patient’s condition.The experimental group had similar treatment as the control group with the addition of traditional Chinese medicine(TCM)acupuncture combined with emotional intervention.The application effects of both groups before and after treatment were verified using the Hamilton Depression Rating Scale(Ham-D),National Institutes of Health Stroke Scale(NIHSS),and Activities of Daily Living(ADL),serotonin levels were measured,and statistical analyses were carried out.Results:The total effective rate of patients in the experimental group was significantly higher than that in the control group,and the Ham-D score,NIHSS score,ADL score,and serotonin level after treatment were significantly higher than those in the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:For patients with PSD,adding TCM acupuncture with emotional intervention on top of conventional treatment significantly improve the clinical efficacy and better improve the daily life ability of patients.

CLINICAL STUDY ON THE TREATMENT OF POST-STROKE DEPRESSION WITH ELECTROACUPUNCTURE OF “NIWAN BAZHEN” POINTS

Objective To observe the therapeutic effect of electroacupuncture （EA） of ＂Niwan Bazhen＂ points in the treatment of post-stroke depression. Methods A total of 66 post-stroke depression patients were randomized into treatment group （EA＋oral administration of Prozac-20, n =31 ） and control group （o- ral administration of Prozac-20, 20 mg/d, 28 days altogether, n =30）. For patients of treatment group, EA （2/100 Hz, a tolerable stimulation strength） was applied to ＂Niwan Bazhen＂ points [Baihui （百会 GV20）, etc. ] for 30 min, once daily, （except weekends） continuously for one month. Halmiton Rating Scale （HAMD） for Depression and Chinese Scale for Stroke （CSS） were used to evaluate the therapeutic effect. Results After the treatment, of the 30 and 31 cases in control and treatment groups, 4 and 6 were cured, 10 and 14 experienced marked improvement.in their symptoms, 6 and 7 had an improvement, 6 and 4 failed, with the cure＋ markedly effective rates being 46.7% and 64.5% respectively. The therapeutic effect of treatment group was significantly superior to that of control group （ P〈0.05）. The decreased values of both HAMD and C,,SS of treatment group were remarkably lower than those of control group （P〈0.01,0.05） . Conclusion EA of ＂Niwan Bazhen＂ points is an effective remedy for post-stroke depression.

The effects of Xingnao Jieyu capsules on post-stroke depression are similar to those of fluoxetine

The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.

miR-137, a new target for post-stroke depression?

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Luciferase assays showed miR-137 bound to the 3＇UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, no- ticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

Electroacupuncture at the Wangu (GB 12) acupoint suppresses expression of inflammatory factors in the hippocampus and frontal lobe of rats with post-stroke depression

Electroacupuncture was performed at the Wangu （GB 12） acupoint, whose position is similar to the cerebellar fastigial nucleus in rats with post-stroke depression. Results showed that the expression of nuclear factor-κB and the levels of tumor necrosis factor-α and interleukin-1β decreased. Simultaneously, the extent of edema in the hippocampus and frontal lobe decreased, and the morphology of the nerve cells recovered to near normal. In addition, fluoxetine treatment displayed a similar effect on post-stroke depression as electroacupuncture at GB 12 acupoint. The results indicate that electroacupuncture at GB 12 acupoint can reduce the levels of cytokines in the hippocampus and frontal lobe of rats with post-stroke depression, and thus provide a neuroprotective effect on post-stroke depression.

Metabolic changes of prefrontal cerebral lobe,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

BACKGROUND： Proton magnetic resonance spectroscopy （IH-MRS） non-invasively detects changes in chemical substances in the brain, which reflects the pathological metabolism.OBJECTIVE： To investigate changes in N-acetyl-aspartate （NAA）, choline （Cho）, creatine （Cr）, and myoinositol （MI） in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression （PSD） using ^1H-MRS. DESIGN： A case control study. SETTING： The First Affiliated Hospital of the Dalian Medical University. PARTICIPANTS： A total of 38 patients with stroke （28 male and l0 female patients, aged 40 to 79 years） were selected from the Department of Neurology, 1st Affiliated Hospital, Dalian Medical University, from February to October in 2004. All subjects met the DSM-IV criteria for cerebrovascular disease and depression. The degree of depression was defined according to Hamilton criteria. 38 patients with PSD were divided into two groups according to the time after ischemia, 20 patients in the acute group with less than 10 days after ischemic attack （mild： 16 patients, moderate/severe： 4 patients） and 18 patients in the chronic group with more than l l days after ischemic attack （mild： 15 patients, moderate/severe： 3 patients）. Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group. The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, and each participant signed an informed consent form. METHODS： Spectra were acquired by multi-voxel point-resolved spectroscopy （PRESS） sequence with GE signal.5T MR/i, localized in prefrontal cerebral lobe and cerebellum. Values of NAA, Cho, MI, and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS 11.5. MAIN OUTCOME MEASURES： Metabolite concentration in different brain regions of interest. Difference in metabolites between distinctly graded PSD patients and control subjects. Exclusion of age-effects on metabolites. RESULTS： Metabolite concentrations of different brain regions： A significant rise in the Cho/Cr ratio was detected in the acute and chronic group compared to the control group. The ratio change was more significant in the acute group （P 〈 0.05）. There was no significant difference between these three groups for other metabolites detected by IH-MRS in the right frontal white matter, bilateral frontal grey matter, and cerebellum （P 〉 0.05）. Comparison of metabolite levels among differently graded PSD patients and control subjects： a significant increase in the Cho/Cr ratio was detected in the left frontal white matter compared to the control group （P 〈 0.05）. There was no significant difference in age between patients in the stroke groups and the control group （P 〉 0.05）, and similarly, there was no significant correlation between age and absolute or relative values in the control group （P 〉 0.05）. CONCLUSION： Abnormalities of frontal lobe in PSD were located in the white matter. There was early abnormality of metabolic substance in PSD.

Clinical Observation of Huatanjieyu Granule in the Treatment of Post-stroke Depression

[Objectives]To observe the clinical effect of Huatanjieyu granule on patients with post-stroke depression.[Methods]Total 76 patients with confirmed post-stroke depression were randomly divided into two groups(treatment group and control group)according to the double-blind principle.The treatment group(38 cases)was treated with Huatanjieyu granule combined with escitalopram,and the control group(38 cases)was treated with escitalopram alone.The course of treatment was 6 weeks.Through clinical efficacy,Hamilton Depression Scale(HAMD)and Treatment Emergent Symptom Scale(TESS)scores were compared,and blood,liver function,renal function and electrocardiogram were examined.[Results]The scores of HAMD and TESS in patients with post-stroke depression were significantly decreased by Huatanjieyu granule,and there were no obvious side effects.The total effective rate was 92.1%in the treatment group and 76.3%in the control group.There was significant difference between the two groups(P<0.01).[Conclusions]Huatanjieyu granule was effective in the treatment of post-stroke depression with little side effects and was easy to be accepted by patients.

CLINICAL STUDY ON ACUPUNCTURE IN THE TREATMENT OF POST-STROKE DEPRESSION WITH THE METHOD OF ACTIVATING THE DU MERIDIAN AND CLEARING THE MIND

Objective: To observe the therapeutic effect of acupuncture in the treatment of post-stroke depression (PSD) with the method of activating the Du Meridian and clearing the mind. Methods: Two hundred and thirty one cases of PSD were randomly divided into two groups, acupuncture and control groups. In acupuncture group, Baihui (百会 GV 20), Dazhui (大椎 GV 14), Neiguan (内关 PC 6), Taichong (太冲 LR 3) and Shenmen (神门 HT 7) were selected as the main points to invigorate flow of qi in the Du Meridian and clear the mind. Patients in the control group received Fluoxetine orally, 20 mg once per-day. In addition, the same routine treatments were given to both groups, strengthened with rehabilitation exercises as early as possible; 8 weeks constituted one therapeutic course. HAMD and severity of neuro-functional defect of each case were evaluated before and 8-week after the treatment. Results: The total effective rate of acupuncture group was 92.37%, the control group, 72.88%. According to χ2 test, the difference between the two groups was remarkably significant (P<0.05). Conclusion: Acupuncture therapy of activating the Du Meridian and clearing the mind in the treatment of PSD was safe and effective.

Role of Transcranial Direct Current Stimulation in the Management of Post-Stroke Depression

Study Objectives: Stroke is a major neurological disease significantly threatening the human health and life with a high morbidity, disability, and mortality. Post-stroke depression (PSD) is one of the common complications of stroke. PSD has been a major factor hindering the recovery of neurological functions and daily activities in stroke patients and is closely related to the social avoidance and increased mortality of stroke patients. Although antidepressant drug treatment has improved during the last decades, symptoms in about 20% of the patients are not in remission two years after initiation of pharmacological intervention. Nowadays, non-invasive brain stimulation;techniques;transcranial direct current stimulation (tCDS) has gained an important interest in the treatment of many neuropsychiatric disorders which might be of some help in treatment of PSD. The goal of the current study is to evaluate the beneficial short term role of tDCS on post-stroke depression. Study Design: This was a randomized double blind placebo-controlled clinical trial included forty hemiparetic patients with post-stroke depression from outpatient clinic of Faculty of Physical Therapy, Cairo University, in the period between June 2018 to June 2019. All patients diagnosed as having a PSD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Depression was evaluated by Hamilton Depression Rating Scale (HAM-D) pre and post treatment and quality of life was evaluated by the Stroke Specific Quality Of Life scale (SS-QOL). Patients were assigned randomly into two groups: the study group A and the control group B. Both groups received antidepressant medication in addition to physical therapy program. Group A received tCDS for 30 minutes, three times per week for one month, while the group B received sham transcranial direct current stimulation. Results: Active tDCS was significantly superior to sham with significant improvement in depression and Stroke Specific Quality Of Life in treated group in comparison to group B, p = 0.000. Conclusion: tDCS was effective for post- stroke depression and might be a favorable option for treating post-stroke patients.

Research Progress in the Pathogenesis of Post-stroke Depression

Post-stroke depression is an affective disorder that occurs after stroke.Its pathogenesis has not yet been fully understood,and it mainly involves neurobiology,neuroanatomy,and psychology.This paper provides an overview on the neurobiological mechanism of post-stroke depression to further understand post-stroke depression and to provide references for further research.

Systematic review and meta-analysis on efficacy of traditional Chinese medicine in treatment of inflammatory factors in patients with post-stroke depression

Objective:To systematically evaluate the effect of traditional Chinese medicine on inflammatory factors in patients with post-stroke depression(PSD)and the efficacy of traditional Chinese medicine on PSD.Methods:Chinese databases(Sinomed,CNKI,VIP,Wanfang),PubMed,Cochrane Library,and Web of Science were searched.Randomized controlled trials of patients with PSD treated with traditional Chinese medicine were included.Quality evaluation was performed and Meta-analysis was performed using RevMan 5.4 software.Results:The results show that TCM therapy is superior to western medicine in reducing the level of TNF-α[MD=-4.13,95%CI(-4.75,-3.51),P<0.00001],IL-6[MD=-3.39,95%CI(-3.90,-2.88),P<0.00001]and IL-8[MD=-2.12,95%CI(-2.49,-1.75),P<0.00001]in venous blood of PSD patients,and is superior to western medicine in reducing the score of HAMD[MD=-4.22,95%CI(-5.37,-3.07),P<0.00001]and NIHSS[MD=-2.33,95%CI(-3.43,-1.23),P<0.0001].The combination of Chinese medicine and western medicine is superior to western medicine in reducing the level of TNF-α[MD=-10.61,95%CI(-15.30,-5.91),P<0.00001]、IL-1[MD=-3.75,95%CI(-4.51,-2.99),P<0.00001]、IL-6[MD=-3.83,95%CI(-4.49,-3.16),P<0.0001]、IL-8[MD=-9.41,95%CI(-14.89,-3.92),P<0.00001]and Hcy[MD=-3.81,95%CI(-4.62,-2.99),P<0.00001]in venous blood of patients with PSD,and is superior to western medicine in reducing the score of HAMD[MD=-3.06,95%CI(-3.39,-2.73),P<0.00001]、NIHSS[MD=-4.47,95%CI(-7.55,-1.39),P=0.004]and HAMA[MD=-2.83,95%CI(-3.47,-2.19),P<0.00001]and improving BI index.Three studies do not mention adverse reactions,and 37 cases in the remaining three studies show rash,tremor,dizziness and other adverse reactions.The incidence of adverse reactions in the experimental group was lower than that in the control group,and there were no serious adverse reactions.Conclusion:The results suggest that traditional Chinese medicine can reduce the level of some inflammatory factors in patients with PSD to a certain extent,and its efficacy is better than that of western medicine alone.Nevertheless,this study has some limitations,and with the increase of related trials in the future,the conclusions of the study need to be further discussed by adding more high-quality RCT studies.

Discussion on the law of acupoint selection by acupuncture in the treatment of post-stroke depression based on the data mining technique

Objective:To analyze the law of acupoint selection in treatment of depression after stroke by using data mining technique,providing reference for clinical treatment.Methods:Through the retrieval of CNKI,wanfang data resource system and Vip Database,relevant literature on acupuncture treatment of this disease in China from the inception of the database to 2019 were collected.Thus the database of acupoint prescriptions was established.SPSS20.0 and SPSS Modeler 18.0 software were used for statistical analysis to explore the law of acupoint selection.Results:A total of 92 articles were selected,92 acupuncture prescriptions and 88 acupoints with a total frequency of 715 times.The frequency of acupoints of Du channel ranked first.The frequency of acupoints in the head and neck and lower limbs were successively 40.42%(289/715)and 20.46%(172/715).Specific acupoints accounted for 81.82%of the acupoints used,among which confluent acupoints ranked first.The correlation analysis results showed that the highest support of acupoint combination was Baihui(GV20)and Shenting(GV24).Conclusion:The acupoint selection in the treatment of PSD gives priority to the Du channel,following the principle of local acupoint selection,local and remote acupoint selection with the precondition of regulation the mind.Attach importance to the use of specific acupoints,especially the confluent points.

Meta-analysis of the relationship between post-stroke depression and the risk of mortality

Objective:To evaluate the relationship between post-stroke depression(PSD)and the risk of mortality in post stroke patients.Methods:Cohort studies related to PSD and risk of mortality were collected by searching PubMed,Cochrane Library,EMBASE,WanFang Data,CNKI and VIP databases.The retrieval time limit was from the establishment of the database to January 2020.The meta-analysis was carried out by Using Stata software after two researchers independently selected literature,extracted data and evaluated the bias risk.Results:A total of 243826 participants were included in 12 studies.The combined results showed that PSD increased all-cause mortality in stroke patients[HR=1.51,95%CI(1.16,1.85),P<0.001].Subgroup analysis also showed that PSD significantly increased all-cause mortality in stroke patients during brief-term follow-up:[HR=1.45,95%CI(0.96,1.93),P<0.001]and long-term follow-up:[HR=1.51,95%CI(1.23,1.79),P<0.001].Conclusion:PSD can significantly increase the risk of mortality in post-stroke patients.Considering the limitation of potential heterogeneity,more high-quality literature studies are needed to verify.

Research progress on pharmacological effect of Salvianolic acid for injection in post-stroke depression

Post-stroke depression (PSD) is one of the most common affective disorders after acute cerebrovascular injury. It significantly increases the mortality, disability rate and recurrence rate of stroke, which places a heavy burden on families and society. The etiology of PSD is not yet clear, involving a series of complex mechanisms. Inflammatory response, apoptosis, neurotrophic factors, neurotransmitters and many others may play important roles, and there is no effective treatment. Salvianolic acid for injection (SAFI) has the functions of anti-inflammatory, anti-oxidative stress, anti-apoptotic and can improve depressive behavior. It is expected to become a new antidepressant for the treatment of PSD.

Sociodemographic profile and social support for post-stroke depression in Kinshasa: A rehabilitation based cross-sectional study

The World Health Organization has highlighted the emergence of non-communicable chronic diseases, including stroke, in developing countries. As a cause of death, stroke ranks first in Africa. Stroke is the foremost cause of neuropsychiatric disease, including post-stroke depression (PSD) which is a very common disease. Surveys of this condition in Congolese pa tients are virtually non-existent. The objectives of this study were to assess the prevalence of PSD in Congolese patients and identify associated sociodemographic factors. Age, sex, address, province of origin, social and professional status, education, religion and consumption habits were chosen as indicators or parameters of interest to be examined in this study. The results of descriptive analyses are presented as frequencies for categorical variables and as mean ± standard deviation for quantitative variables. The association between different variables was assessed using tables of comparisons of proportions and the Chi-square test. Logistic regression was performed to predict the occurrence of PSD. There were more male than female patients. The mean age was 54.67 ± 12.51 years. Nearly 3 fourths of the patients were aged less than 65. The family was the primary source of social support. The majority was satisfied by the social support received from the family. Just over half the study patients (53.6%) had mild to severe depression as assessed by the PHQ9. Univariate analysis and logistic regression indicated a statistically significant association between low educational level and the occurrence of PSD. However, there was no relationship between age, sex or drinking habits and the onset of PSD. The majority of the subjects were satisfied by the social support from their families. Depression was common after stroke with the occurrence of 53.6%. These results highlight the need to investigate, diagnose and treat PSD, which is a risk factor for morbidity and mortality after stroke.

Progress of Traditional Chinese Medicine in the Treatment of Post-stroke Depression

The patients with post-stroke depression often form a negative evaluation of themselves,and even have the idea of suicide in serious cases.Therefore,post-stroke depression has become one of the most common complications of mental illness after stroke,which seriously hinders the normal rehabilitation of the central nervous system,thus increasing the disability rate,early recurrence rate and mortality rate of patients.Therefore,the active treatment of post-stroke depression is very necessary.Western medicine uses antidepressant drugs for this kind of patients,but because the side effects of antidepressants are relatively large,the compliance of patients is not good,it is not easy to see the effect,while traditional Chinese medicine(TCM)has many ways to deal with post-stroke depression with obvious advantages,the side effects are relatively small,and there is more compliance in patients.This paper focuses on several TCM treatment methods,hoping to provide a reference for the treatment of post-stroke depression.

Melatoninergic Antidepressant in Post-Stroke Depression Therapy

This paper presents the results of the effects of Melitor (25 mg during two months) on the psychic-emotional state, cerebral hemodynamic and bioelectrical activity of the brain in 30 patients (average age 66.2 ± 3.2 years) with ischemic post-stroke depression. It has been found that this drug possesses a multimodal action which is characterized by the decrease of the level of depression, widening of the range of social-environmental activity, improvement of the cerebral blood circulation and harmonization of the brain electrogenesis. In the patients with right versus left hemisphere stroke, the effect of Melitor on the functional state of the brain was more pronounced. Based on the results obtained in our study, we can recommend Melitor to use it in complex scheme of rehabilitation care of patients of the given nosological category.

Effect of different therapies of Chinese medicine on the expressions of c-Fos and c-Jun proteins in hippocampus of rats with post-stroke depression

BACKGROUND ： c-fos and c-jun, the important immediate early genes （IEG）, are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression. OBJECTIVE： To observe the therapeutic effects of Bushen Yiqi （tonifying kidney to benefit qi）, Huoxue Huayu （promoting blood circulation to dissipate blood stasis） and Ditan Kaiqiao （eliminating phlegm for resuscitation） on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression （PSD）, and compare the results with those of fluoxetine, which is known to have definite effect on depression. DESIGN： A randomized controlled tna SETTING ： Zhejiang College of Traditional Chinese Medicine MATERIALS ： The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing （250±50） g, were randomly divided into 7 groups with 8 rats in each group： control group, model group, forced swimming group, Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang contained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Ditan Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/b METHODS： ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid artedes permanently. ② Rats in the control group, model group and forced swimming group were intragastncally perfused by saline （3 mL for each time）; those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group were intragastncally perfused with Bushen Yiqi Tang （18 g/kg）, Huoxue Huayu Tang （9 g/kg）, Ditan Kaiqiao Tang （9 g/kg） and fluoxetine （2.5 mg/kg） respectively, once a day. ③ At 55 days after model establishment, rats in the forced swimming group were managed according to the Porsolt＇s method. They were placed in water for 15 minutes, and then taken out and dned, no moving-time within 5 minutes was recorded at drying and 24 hours after drying. ④ Measurement of spontaneous behaviors： Except the forced swimming group, the spontaneous behaviors and activities （including horizontal and vertical movements） of rats were observed with the Open-Field method at 28, 42 and 56 days after administration in the other groups. ⑤ The expressions of c-Fos and coJun proteins in hippocampus were determined with the immunohistochemical method, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hip- pocampus were measured with the computerized image analytical system. MAIN OUTCOME MEASURES： The spontaneous behaviors of rats, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hippocampus were observed. RESULTS： Of the 56 rats, 1 died in the forced swimming group, and finally 55 rats were involved in the analysis of results. ① Results of spontaneous activities： At 28 days, the times of crossing movements were obviously fewer in the model group and fluoxetine group [（69.00±37.01）, （98.11 ±36.68） times/3 minutes] than in the control group [（128.44±16.85） times/3 minutes, P 〈 0.01, 0.05], but those in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group had no obvious differences as compared with those in the control group （P 〉 0.05）. At 42 and 56 days, the times of crossing movements were obviously more in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group [（106.44±31.24）, （117.20±23.95）, （134.80±28.18）, （136.36±40.95） times/3 minutes; （117.33±35.91）, （129.60 ±23.78）, （131.90 ±26.81）, （136.09±28.34） times/3 minutes] than in the model group [（64.00±17.51）, （72.86±20.68） times/3 minutes, P 〈 0.01]. The times of rearing movements had no obvious differences among the groups for the three times （P 〉 0.05）. ② The no moving-time within 5 minutes 24 hours after drying was obviously longer than that at drying in the forced swimming group. ③ The average objective gray values of c-Fos positive cells were not obviously different in the Bushen Yiqi group and Ditan Kaiqiao group from the control group （P 〉 0.05）, but lower in the model group than in the control group （69.84±9.82, 75.78±5.89, P 〈 0.01）, and higher in the forced swimming group than in the control group （85.97±10.99, P 〈 0.01）; all higher in the fluoxetine group, Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group （81.27±10.73, 74.04±8.34, 83.29±9.89, 70.14±4.92, P 〈 0.05-0.01）. The average objective gray values of c-Jun positive cells were obviously lower in the Bushen Yiqi group than in the control group （68.11 ±6.89, 79.58±5.86, P 〈 0.01）, but all higher in the other groups than in the control group （84.68±7.15, 81.34 ±8.36, 97.51±10.55, 85.68±9.25, 86.19±10.98, P 〈 0.05-0.01）; Those were obviously higher in the fluoxetine group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group （P 〈 0.05-0.01 ）, lower in the Bushen Yiqi group than in the model group （P 〈 0.05）, all obviously lower in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the fluoxetine group （P 〈 0.01）. The relative sectional area ratios of c-Fos and c-Jun positive cells had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： The methods of Bushen Yiqi, Huoxue Quyu and Ditan Kaiqiao can effectively treat PSD in rats, and the results were equivalent with those of fluoxetine, the actions of the above-mentioned drugs may correlated with their regulation to c-Fos and c-Jun expressions in hippocampus. PSD animal models can be successfully established by both permanent deligation of bilateral common carotid arteries and forced swimming, and the models induced by the former has similar basic cerebrovascular lesions as human stroke in clinic.