Research Progress in the Treatment of Poststroke Depression with Traditional Chinese Medicine

In recent years,the incidence rate of stroke has increased year by year.Post stroke depres‐sion is one of its main complications,which seriously affects the recovery of physiological functions and quality of life of stroke patients.Traditional Chinese medicine has signifi‐cant therapeutic effects in treating this disease.This article provides a classification and review of traditional Chinese medicine treatment methods for post-stroke depression,and looks forward to the current problems.

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.

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.

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.

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.

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 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.

Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(银杏蜜环口服溶液) attenuates inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in post stroke depression

OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃emic cardiovascular and cerebral vascular diseases.Recently,it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders,such as post stroke depression(PSD)and chronic heart disease(CHD)associated anxiety disorder.However,its mechanism has not been clearly elucidated.Meanwhile,increasing evidence revealed that there are close functional links between depression and habenular nucleus.The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in in a rat model of PSD.METHODS Rats were randomly devided into sham group,model group,Ginaton group(18 mg·kg^-1),Armillariella Mellea group(600 mg·kg-1),Fluoxetine group(10 mg·kg^-1),YXMH high-dose group(618 mg·kg^-1)and YXMH low-dose group(309 mg·kg^-1).The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine,PCPA,IH,200 mg·kg^-1,for 3 times,before the behavior test)in SD male rats.Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later,followed by body mass measurement,neurological deficit score evaluation,gripping strength and thermal withdrawl latency measurement,as well as depression related behavioral indicators,the open field test(OFT)and sucrose preference test.The pathological morphological changes of habenular nucleus was observed by HE staining,the expression of IBA-1 was measured and analyzed by immunohistochemistry staining,and alterations of proteins and genes related to the CX3CL1-CX3CR1 axis were analyzed using Western blotting(CX3CL1,CX3CR1)and real-time polymerase chain reaction(PCR)(CX3CL1,CX3CR1).RESULTS Compared with the sham group,rats in the model group manifested as decreased body mass,deficient neurological behavior and gripping strength,reduced loco⁃motor activity and sugar water consumption,as well as elevated thermal withdrawl latency(P<0.05,P<0.01).Mean⁃while,the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration,microglial proliferation,inflammatory cells and glia cells infiltration,together with up-regualted expression of IBA-1,CX3CL1,CX3CR1 protein and CX3CL1,CX3CR1 mRNA.YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology,inhibiting IBA-1 activation,down-regulating the expres⁃sion of CX3CL1 and CX3CR1 proteins and genes,and thus improved the behavior performance of ischemic injury and depression.CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation,and the mechanism is probably related to attenu⁃ating inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis.

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.

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.

Predictive power of abnormal electroencephalogram for post-cerebral infarction depression

Electroencephalography is a sensitive indicator for measuring brain condition, and can reflect early changes in brain function and severity of cerebral ischemia. However, it is not yet known whether electroencephalography can predict development of post-cerebral infarc- tion depression. A total of 321 patients with ischemic stroke underwent electroencephalography and Hamilton Depression Rating Scale assessment to analyze the relationship between electroencephalography and post-cerebral infarction depression. Our results show that electroencephalograms of ischemic stroke patients with depression exhibit low-amplitude alpha activity and slow theta activity. In con- trast, electroencephalograms of ischemic stroke patients without depression show fast beta activity and slow delta activity. ＂Ihese findings confirm that low-amplitude alpha activity and slow theta activity can be considered as independent predictors for post-cerebral infarction depression.

基于认知-行为的多层次护理对卒中后抑郁的效果影响

目的探讨基于认知-行为的多层次护理干预对卒中后抑郁(post-stroke depression,PSD)的效果影响。方法选择武汉科技大学附属天佑医院神经内科2019年1月—2023年1月住院的110例PSD患者作为研究对象,对上述患者入院的前后顺序进行标号,随机分为2组,对照组(n=55)予以常规护理措施干预,在此基础上观察组(n=55)予以基于认知-行为的多层次护理干预。2组患者干预前和干预后1个月,分别采用汉密尔顿抑郁量表(Hamilton depression scale,HAMD)、汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)、简易精神状态检查量表(mini-mental state examination,MMSE)、Barthel指数(barthel index,BI)、生活质量综合评定问卷-74(generic quality of life inventory 74,GQOLI-74)评估患者的精神症状、认知状况、日常生活能力、生活质量。结果与观察组护理干预前和对照组干预后比较,观察组护理干预后HAMD(16.01±1.97)分、HAMA(14.37±1.48)分均明显降低(P<0.05);观察组护理干预后MMSE(28.74±3.16分)、BI(83.09±7.81分)及生活质量评分均明显升高(P<0.05)。结论基于认知-行为的多层次护理干预可明显改善PSD患者的精神症状、认知状况及日常生活能力,同时生活质量也得到明显地提高。

TLR4/miR-223/NLRP3信号通路的表达与脑卒中后抑郁大鼠海马炎症反应的关系

目的探究Toll样受体4(TLR4)/miR-223/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路的表达与脑卒中后抑郁(PSD)大鼠海马炎症反应的关系。方法30只3月龄SPF级健康雄性Sprague-Dawley大鼠分为假手术组,PSD模型组和TLR4抑制剂组,各10只。PSD模型组和TLR4抑制剂组建立PSD模型,TLR4抑制剂组给予0.3 mg/kg的TAK-242溶液腹腔注射,其余各组均腹腔注射等体积的生理盐水溶液,5次/周,连续4周。评定各组大鼠的神经行为学,ELISA法检测血清白介素-1β(IL-1β)和IL-10的表达水平,RT-PCR测定海马组织中TLR4/miR-223/NLRP3信号通路相关基因的表达,Western blot测定TLR4/miR-223/NLRP3信号轴蛋白的相对表达。结果与假手术组相比,PSD模型组和TLR4抑制剂组大鼠Longa评分以及血清IL-1β和IL-10的表达升高,糖水偏嗜比(SP)、移动情况(LA)显著降低(P<0.05);与PSD模型组相比,TLR4抑制剂组大鼠Longa评分以及血清IL-1β和IL-10的表达表达下降、LA和SP升高(P<0.05)。与假手术组相比,PSD模型组大鼠海马组织中TLR4 mRNA、miR-223和NLRP3 mRNA以及TLR4、NLRP3、IL-1β和IL-10蛋白的相对表达均显著升高(P<0.05);与PSD模型组相比,TLR4抑制剂组的TLR4 mRNA和NLRP3 mRNA以及TLR4、NLRP3、IL-1β和IL-10蛋白的相对表达显著降低,miR-223的表达显著升高(P<0.05)。结论TLR4/miR-223/NLRP3信号转导通路与PSD海马炎症反应密切相关,通过调控TLR4/miR-223/NLRP3信号转导通路可能成为临床防治PSD的新靶位和新思路。

醒神解郁汤联合针刺对老年卒中后抑郁患者的疗效及对血清5-HT、NE的影响

目的探讨醒神解郁汤联合针刺对老年卒中后抑郁患者的疗效及对血清5-羟色胺(5-HT)、去甲肾上腺素(NE)的影响。方法选取2020年1月-2021年4月本院收治的96例老年卒中后抑郁患者,采用随机数字表法分为对照组和研究组,各48例。2组均给予基础治疗,对照组另给予草酸艾司西酞普兰片,研究组另给予醒神解郁汤联合针刺治疗。对比2组治疗前后中医症状评分、汉密尔顿抑郁量表(HAMD)及美国国立卫生院神经功能缺损评分(NIHSS)评分、临床疗效。对比2组治疗前后血清5-HT、NE水平。对比2组治疗期间安全性。结果治疗后2组主症、次症评分及总分均下降(P<0.05),治疗后研究组主症、次症评分及总分均低于对照组(P<0.05)。与治疗前相比,治疗后2组HAMD评分、NIHSS评分均降低(P<0.05),研究组治疗后HAMD评分、NIHSS评分均低于对照组(P<0.05)。2组临床疗效比较差异具有统计学意义(P<0.05),且研究组总有效率高于对照组(P<0.05)。与治疗前比较,治疗后2组血清5-HT、NE升高,且研究组高于对照组(P<0.05)。2组不良反无统计学意义(P>0.05)。结论醒神解郁汤联合针刺治疗老年卒中后抑郁患者可缓解患者临床症状,有效降低抑郁症状及神经功能缺损评分,提高临床疗效,调节单胺类神经递质水平,且安全可靠。

基于网络药理学-分子对接技术研究柴胡治疗卒中后抑郁的药效物质基础及作用机制

目的:通过网络药理学和分子对接技术,探讨柴胡治疗卒中后抑郁(Post-stroke Depression,PSD)的潜在活性成分和可能的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)和蛋白质序列数据库(Uniprot)筛选出柴胡主要活性成分及其靶点基因,并将目标蛋白名称标准化,通过GeneCards、OMIM数据库获取PSD靶点基因;对两者靶点取交集后采用STRING数据库构建柴胡治疗PSD的潜在靶点的蛋白质-蛋白质相互作用网络图;利用Cytoscape-v3.9.1软件进行核心靶点筛选;利用DAVID数据库对潜在靶点进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。最后,利用PyMol软件和AutoDockTools-1.5.7软件对柴胡主要活性成分与核心靶点使用分子对接技术绘制相应的分子对接图。结果:共筛选得到柴胡活性成分17个,去重后对应靶点175个,疾病靶点852个,经Venny数据库预测到疾病-药物交集靶点45个。GO功能富集分析结果显示共获得323个GO功能注释,KEGG通路富集分析结果显示获得106条信号通路。分子对接结果显示,牵牛花色素与糖原合成酶激酶3β(Glycogen Synthase Kinase 3 Beta,GSK3B),异鼠李素与雌激素受体1(Estrogen Receptor 1,ESR1)、GSK3B,山柰酚与半胱氨酸蛋白酶(Caspase 3,CASP3),槲皮素与白细胞介素-10(Interleukin-10,IL-10)、基质金属蛋白酶9(MatrixmetalloProteinase 9,MMP9)、胰岛素样生长因子结合蛋白3(Insulin Like Growth Factor Binding Protein 3,IGFBP3)、CASP9均结合稳定。结论:柴胡活性成分牵牛花色素、异鼠李素、山柰酚、槲皮素,可能通过脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等信号通路作用于GSK3B、ESR1、CASP3、IL-10、MMP9、IGFBP3、CASP9等核心靶点,发挥治疗PSD的疗效,初步预测了柴胡对PSD的作用机制。

Anti-depressant effects of Jieyu Anshen granule in chronic unpredictable mild stress-treated rats after ischemic stroke

OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule(JY) in chronic unpredictable mild stress(CUMS)-treated rats after ischemic stroke.METHODS A rat model of post-stroke depression(PSD) was developed by additional CUMS procedures after middle cere.bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg^(-1) and 3 g·kg^(-1) of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg^(-1)) served as a reference drug.Behavioral tests including sucrose preference test,forced swim test and open-field test were performed to evaluate the antidepressant effects.Levels of norepinephrine(NE),dopamine(DA) and 5-hydroxytryptamine(5-HT) in rat brain were assayed.The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain.Serum adrenocorticotropic hormone(ACTH) and corticosterone(CORT) were estimated as indices of hypothalamic-pituitary-adrenal(HPA) axis activity.Western blot analysis was used to evaluate hippo.campal expression of the 5-HT1 A receptor(5-HT_(1A)R) and brain-derived neurotrophic factor(BDNF).RESULTS PSD rats exhibited decreased sucrose consumption and motor activity,increased immobility time(P<0.01).JY treatment reversed the depressive behaviors in PSD rats(P<0.05,P<0.01).Treat.ment with JY resulted in significantly increased levels of NE,DA and 5-HT in the hippocampus and prefrontal cortex(P<0.05,P<0.01),and increased expression of 5-HT_(1A)R and BDNF in the hippocampus(P<0.01).JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus and prefrontal cortex(P<0.05).Treatment with JY also resulted in significantly decreased ACTH and CORT in serum which had been increased(P<0.05).CONCLUSION These findings suggest that JY treat.ment could ameliorate PSD,and the effects are likely ascribed to inhibiting HPA axis hyperfunction and inflammatory,up-regulating the levels of neurotransmitters(NE,DA and 5-HT),and the expression of hippocampal 5-HT_(1A)R and BDNF.

“通督治郁”针法治疗脑卒中后抑郁对临床症状及血清5-HT、NE、DA的影响

目的观察“通督治郁”针法治疗脑卒中后抑郁(PSD)对临床症状及血清5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)的影响。方法选取2022年1月—2023年1月医院收治的60例PSD患者作为研究对象,按随机数字法分为对照组和观察组各30例,两组均给予脑卒中常规治疗,对照组采用常规针刺联合度洛西汀胶囊抗抑郁治疗,观察组采用常规针刺联合通督治郁针法治疗,比较两组临床疗效、中医证候积分、汉密顿抑郁量表(HAMD)评分、美国国立卫生院神经功能缺损评分(NIHSS)、Barthel指数、神经细胞因子[脑源性神经营养因子(BDNF)、神经生长因子(NGF)]、单胺类神经递质(5-HT、NE、DA)及不良反应发生率。结果两组治疗有效率比较差异无统计学意义(93.33%vs 80.00%)(P>0.05)。治疗后,两组中医证候积分、HAMD评分、NHISS评分均降低,Barthel指数和血清BDNF、NGF、5-HT、NE、DA水平均升高(P<0.05);且观察组NHISS评分均显著低于对照组,Barthel指数和血清BDNF、NGF水平均显著高于对照组(P<0.05),两组中医证候积分、HAMD评分及血清5-HT、NE、DA水平比较差异无统计学意义(P>0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论“通督治郁”针法和口服度洛西汀胶囊治疗PSD疗效相当,均可有效缓解抑郁症状,提高单胺类神经递质的合成释放,但前者在促进神经功能康复等方面优于后者,值得临床推广应用。

符为民教授基于“六腑以通为用”与脑-肠轴理论治疗卒中后抑郁经验

卒中后抑郁是抑郁的一种特殊存在形式,严重影响脑卒中患者神经功能的恢复及回归社会的能力。符为民教授认为其病机为脏腑气机失调,痰浊瘀血内生,脑腑功能失调。基于“六腑以通为用”中医理论,符教授提出以通腑为治疗大法,临证时常根据疾病的不同阶段,精准辨证,采用通腑降气、泻心通腑、化痰通气、活血通腑、醒脑通腑等不同“通”法,临床疗效显著。

帕利哌酮调控miR-10a/BDNF通路对卒中后抑郁大鼠的影响

目的:探讨帕利哌酮对卒中后抑郁(PSD)大鼠抑郁行为的改善作用及对微小核糖核酸-10a(miR-10a)/脑源性神经营养因子(BDNF)通路的影响。方法:取SD大鼠,随机分为正常对照组、模型组、帕利哌酮组(1.00 mg/kg)、ad-miR-10a组(尾静脉注射miR-10a过表达腺病毒,每只100μL)、ad-NC组(尾静脉注射不含miR-10a过表达腺病毒质粒空载体溶液,每只100μL)、帕利哌酮+ad-miR-10a组,每组10只。采用大脑中动脉线栓栓塞法+慢性轻度不可预见性应激法建立大鼠PSD模型。各组连续给药4周后,检测大鼠神经功能缺损、肢体运动功能、抑郁样行为。取海马组织,尼氏染色及脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测神经元形态及凋亡状况;免疫组化法检测BDNF阳性表达水平;实时荧光定量聚合酶链式反应(RT-qPCR)法检测miR-10a表达;蛋白免疫印迹法(Western Blot)检测酪氨酸受体激酶B(TrkB)、磷酸肌醇3激酶(PI3K)、凋亡相关蛋白半胱天冬酶-3(Caspase-3)、核糖体蛋白S6激酶α(RPS6KA1)蛋白表达水平。结果:PSD大鼠出现神经功能缺损、肢体运动功能障碍及抑郁样行为,海马组织中神经元损伤及凋亡加重,miR-10a表达升高,BDNF及其介导的抗神经元凋亡相关蛋白表达降低(P<0.05)。帕利哌酮可缓解PSD大鼠抑郁样行为,抑制神经元凋亡及损伤,并下调海马组织中miR-10a表达,促进BDNF及其介导的抗凋亡相关蛋白表达(P<0.05)。上调miR-10a可逆转帕利哌酮的上述作用。结论:帕利哌酮可通过下调miR-10a表达,激活BDNF通路,抑制PSD大鼠海马神经元细胞损伤凋亡,发挥抗抑郁作用。