目的 探讨解郁安神颗粒(JY)对卒中后抑郁(PSD)小鼠模型的抗抑郁作用。方法 将雄性昆明种小鼠随机分为正常对照组、模型对照组、艾司西酞普兰组(5 mg·kg-1)及JY小、中、大剂量组(JY 0.75,1.50,3.00 g·kg-1),每组12只。采用双侧颈总动脉线栓再灌注制备脑缺血小鼠模型,给予慢性不可预知性温和刺激制备PSD小鼠模型。艾司西酞普兰及JY灌胃给药,每天1次,连续给药28 d。通过悬尾实验及强迫游泳实验评价JY对PSD小鼠抑郁行为的影响。采用高效液相色谱法检测PSD小鼠海马去甲肾上腺素(NE)、多巴胺(DA)及5-羟色胺(5-HT)水平。采用Western blotting 检测PSD小鼠海马5-羟色胺1A受体(5-HT1AR)表达。结果 与正常对照组比较,模型对照组小鼠悬尾及游泳不动时间明显增加(
Objective To investigate the antidepressant effect of
PSD的发病机制尚不明确。经典的单胺递质假说认为PSD的发生与去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)及5-羟色胺(5-hydroxytryptamine,5-HT)单胺递质的水平降低密切相关[6]。此外,5-羟色胺1A受体(5-HT1A receptor,5-HT1AR)在大脑海马内分布最为广泛,且与抑郁发生密切相关,是临床抑郁症药物治疗的重要靶点[7]。目前临床上以选择性5-羟色胺再摄取抑制药(selective serotonin reuptake inhibitor,SSRIs)为一线用药,例如西酞普兰、氟西汀等[8,9]。解郁安神颗粒(
无特定病原体(SPF)级昆明种小鼠,雄性,8周龄,体质量30~35 g,由济南朋悦实验动物繁育公司提供,许可证号:SYXK(鲁)20140007。自由摄食和饮水,饲养环境22~24 ℃,相对湿度为40%~60%。
JY(通化利民药业集团有限公司,规格:每袋5 g,批号:140607;艾司西酞普兰片(丹麦灵北药厂生产,西安杨森制药有限公司分装,规格:每片10 mg,批号:151218117);水合氯醛(国药集团化学试剂有限公司,批号 :20130426);羧甲基纤维素钠(天津市科密欧化学试剂有限公司,批号:20110809)。去甲肾上腺素(norepinephrine,NE)(批号:100169-201404)、DA(批号:100070-201507)及5-HT(批号:111656-200401)对照品均购自中国食品药品检定研究院。
PSD小鼠模型参照相关文献[10,11],采用双侧颈总动脉线栓再灌联合慢性不可预知性温和刺激(chronic unpredicted mild stress,CUMS)制备。具体操作:动物用乌拉坦麻醉后固定,颈部用聚维酮碘消毒,在其正中线作一纵行切口,钝性分离皮肤以及皮下组织,分离双侧颈总动脉,用止血钳夹闭双侧颈总动脉阻断血流5 min,随后松开止血钳使血复灌10 min,再次用止血钳夹闭双侧颈总动脉阻断血流5 min,随后松开止血钳,将切口缝合,消毒操作区域。在脑缺血后第2天起,进行CUMS以建立PSD模型,包括:4 ℃ 冰水游泳、过夜照明、禁水、禁食、夹尾、潮湿垫料及合笼。共计7种刺激方法。每天1或2种,连续刺激18 d。除正常对照组外,将PSD模型小鼠随机均分为模型对照组,艾司西酞普兰组(5 mg·kg-1),JY 小、中、大剂量组(JY0.75,1.50及3.00 g·kg-1 ),每组12只。正常对照组及模型对照组给予空白溶媒(0.5%羧甲基纤维素钠),其余各组每日灌胃给药1次,连续给药28 d,给药体积均为10 mL·kg-1。
1.4.1 强迫游泳实验 实验在第20天进行。正式实验前小鼠在实验室首先适应环境至少1 h,然后将小鼠放入强迫游泳实验装置(高35 cm,直径15 cm的透明圆柱形桶,水深35 cm),使小鼠在水中前爪攀附于缸壁,并且不能以后爪支撑身体为标准,15 min后取出动物。正式实验时,将动物置于强迫游泳实验装置,保持水温(25±2) ℃。观察6 min,记录后5 min内累计不动时间。
1.4.2 悬尾实验 实验在第21天进行。采用小鼠专用悬尾箱(30 cm×30 cm×40 cm,内有固定吊环),距尾尖2 cm处用医用胶布固定于吊环上,使其头部距离地面15 cm。实验时悬挂6 min,记录累计不动时间。
给药结束后,将小鼠处死,取脑,于冰上迅速剥离海马组织,称湿重,以1:9加入0.01 mol·L-1磷酸盐缓冲液(PBS),充分匀浆,再向匀浆液中加入其二分之一体积的6%高氯酸,充分涡旋, 4 ℃下16 000 r·min-1离心20 min(
色谱条件:色谱柱为SHIMADZU VP-ODS C18柱(250 mm× 4.6 mm,5 μm);水相为0.01 mol·L-1醋酸钾缓冲液,流动相为甲醇-水(10:90),用0.2 mol·L-1柠檬酸调pH值至4.0等度洗脱;柱温为25 ℃;流速为1.0 mL·min-1;检测波长:275 nm。NE,DA及5-HT的保留时间分别为3.37,5.02及10.08 min。
实验结束后,将小鼠处死,取脑,于冰上迅速剥离海马组织,称取海马组织20 mg,加入RIPA裂解液250 μL,于冰上匀浆,4 ℃下12 000 r·min-1离心5 min(
采用SPSS 20.0版统计软件分析处理数据,计量资料以均数±标准差(
$\bar{x}\pm{s}$)表示。单因素方差分析进行统计处理,以
2.1.1 JY对PSD小鼠游泳不动时间的影响 见
2.1.2 JY对PSD小鼠悬尾不动时间的影响 见
见
PSD是发生于卒中之后的郁证,是在卒中基础上出现以情绪低落、兴趣减少、缺乏主动性、悲观、失望、食欲不振等症状[12]。中医学将其归属“郁证”与“卒中”之合病,该病病因为肝郁气滞,病理基础为肝肾衰弱,病理特点为肝肾下虚,风痰阻络[13]。西医对PSD的发病机制尚不明确,目前普遍接受包括神经内分泌机制和社会心理学机制[14]。抗抑郁药物可以快速有效地治疗PSD,显著改善患者的认知和预后,已成为治疗PSD的重要手段[15]。SSRIs是PSD的治疗首选药物,但大都需2~4周才能充分显效,且存在一定不良反应。中医药近年来在治疗PSD方面卓有成效,且因不良反应少易被人们接受。
PSD动物模型目前多采用卒中伴抑郁的复合模型,经典制备方法为结扎(或线栓)后联合CUMS模型,符合人脑卒中后抑郁的病理特点[16]。因此本研究采用双侧颈总动脉线栓再灌注法制备脑缺血小鼠模型,再给予CUMS联合制备PSD小鼠模型,其表现出绝望等抑郁核心症状。
绝望情绪是PSD患者临床表现的重要症状[17]。强迫游泳和悬尾实验是抑郁样行为学中评价药物抗抑郁作用的经典方法[18]。强迫游泳实验是利用动物无法逃脱水淹而诱导产生绝望行为,悬尾实验是利用动物无法克服不正常体位而诱导产生绝望行为,二者使动物产生绝望情绪的机制有一定差别[19]。本研究中,PSD小鼠在挣扎后表现出不动状态,其“无助”的行为程度能够反映其绝望状态。因此,在悬尾实验中,通过对PSD小鼠不动状态的行为学检测,包括游泳不动时间和悬尾不动时间,评价动物的抑郁样行为。本研究发现,艾司西酞普兰及JY均能明显减少PSD小鼠的游泳不动时间及悬尾不动时间。因此,艾司西酞普兰及JY均能明显逆转PSD小鼠的绝望情绪。
PSD发病机制中经典假说为单胺类递质系统失衡假说,即单胺类神经递质系统功能低下,尤其是NE及5-HT等单胺类递质水平的低下[20,21]。海马是参与调节情感、认知、行为的重要中枢[22]。NE、5-HT及DA作为中枢系统极其重要的神经递质,均可参与情感、情绪、行为、痛觉及睡眠等多项生理功能的调节[23]。以往研究发现PSD大鼠海马组织5-HT、NE 及DA水平与正常大鼠及单纯卒中大鼠比较均显著降低[24]。5-HT1AR主要分布于与情感调节密切相关的边缘系统(尤其分布于海马神经元和齿状回的突触后膜),其功能异常与PSD的发生密切相关[22]。据报道[25],与正常动物比较,抑郁动物模型的海马5-HT1AR表达显著降低,抗抑郁药能够通过上调抑郁动物海马5-HT1AR表达发挥抗抑郁的作用。本研究发现,PSD小鼠海马5-HT1AR表达明显降低,而JY能够明显上调其海马5-HT1AR表达,表明JY发挥抗抑郁的作用应与上调其海马5-HT1AR表达有关。
综上所述, JY对PSD小鼠的抑郁样行为具有明显的改善作用,可明显逆转PSD小鼠的绝望情绪,同时PSD小鼠海马NE等单胺类神经递质水平及5-HT1AR表达明显升高,说明JY对PSD小鼠模型具有抗抑郁的作用,其抗抑郁作用可能是通过提高海马NE、DA及5-HT水平,以及上调海马5-HT1AR表达来实现的。
The authors have declared that no competing interests exist.
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Background Approximately 15 million people who suffer a stroke globally each year are at risk of developing depression. Aim To update our systematic review and meta-analysis of the frequency of depression after stroke published in 2005, including studies published before July 2004. Methods We included all published observational studies (to 31 May 2013) with prospective consecutive recruitment and quantification of the proportion of people with depression after stroke. We included studies of adult (>18 years) patients with a clinical diagnosis of stroke, where an assessment of depression or depressive symptom burden was performed at a pre-specified time-point for all study participants. Results <p>Data were available from 61 studies including 25 488 people. The proportional frequency of depression varied considerably across studies; however, the pooled frequency estimate of 31% (95% confidence interval 28% to 35%) was not significantly different from the 33% (difference of 2%, 95% confidence interval Conclusion Despite systematic review evidence describing validated depression screening tools and effective treatment and prevention strategies for depression after stroke, there has not been a significant reduction in the proportion of people experiencing depression after stroke. There is a pressing need for increased clinical uptake of evidenced-based strategies to screen for, prevent, and treat depression after stroke.
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[5] |
脑卒中后抑郁(post-stroke depression,PSD)是发生于中风之后的郁证,是在中风表现的基础上出现以情绪低落、兴趣减少、缺乏主动性、悲观、失望、食欲不振等症状.研究表明,脑卒中后抑郁增加脑血管病的病死率,阻碍神经及认知功能康复,严重影响患者的生活质量[1].本文就脑卒中后抑郁中药治疗进行综述.
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[6] |
目的观察乌灵胶囊对卒中后抑郁(post-stroke depression,PSD)的一级预防作用。方法将急性脑卒中患者,采用随机化方法分两组。两组在心脑血管病治疗相同基础上,试验组(55例)加服乌灵胶囊(每粒0.33 g)每次3粒,1日3次;对照组55例,加服安慰剂每次3粒,1日3次;2周为1个疗程。每2周进行PSD诊断,符合PSD停服药物;不符合PSD继续服药;持续服药1~12个疗程(共计6个月),若仍不符合PSD,则停止服药。观察PSD发病率、出现抑郁的时间、汉密尔顿抑郁量表(HAMD)评分及不良反应。结果试验组PSD发病率1、3、6个月时分别为8%、16%和34%,对照组分别为19.6%、29.4%和54.9%,试验组发生率均低于对照组,且6个月时比较,差异有统计学意义(χ2=4.465, P〈0.05)。试验组发生PSD平均时间为(14.96±8.31)周,对照组为(9.36±6.06)周,两组比较,差异有统计学意义(t=6.762, P〈0.05);随访6个月,试验组发生PSD时的HAMD评分为(11.96±2.14)分,对照组为(14.57±4.24)分,两组比较,差异有统计学意义(t=5.641, P〈0.05)。结论乌灵胶囊在降低PSD发病率、延缓PSD发生时间、减轻 PSD发生抑郁程度方面均优于安慰剂组,对PSD有一定的预防作用。
[本文引用:1]
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[7] |
DOI:10.1159/000355145
URL
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Abstract OBJECTIVE: To ascertain the prevalence and predictors of mood disorders, determined by structured clinical interviews (ICD or DSM criteria) in people after stroke. METHODS: Major electronic databases were searched from inception to June 2016 for studies involving major depression (MDD), minor depression (MnD), dysthymia, adjustment disorder, any depressive disorder (any depressive disorder) and anxiety disorders. Studies were combined using both random and fixed effects meta-analysis and results were stratified as appropriate. RESULTS: Depression was examined on 147 occasions from 2days to 7years after stroke (mean 6.87months, N=33 in acute, N=43 in rehabilitation and N=69 in the community/outpatients). Across 128 analyses involving 15,573 patients assessed for major depressive disorder (MDD), the point prevalence of depression was 17.7% (95% CI=15.6% to 20.0%) 0.65 analyses involving 9720 patients determined MnD was present in 13.1% in all settings (95% CI=10.9% to 15.8%). Dysthymia was present in 3.1% (95% CI=2.1% to 5.3%), adjustment disorder in 6.9% (95% CI=4.6 to 9.7%) and anxiety in 9.8% (95% CI=5.9% to 14.8%). Any depressive disorder was present in 33.5% (95% CI=30.3% to 36.8%). The relative risk of any depressive disorder was higher following left (dominant) hemisphere stroke, aphasia, and among people with a family history and past history of mood disorders. CONCLUSION: Depression, adjustment disorder and anxiety are common after stroke. Risk factors are aphasia, dominant hemispheric lesions and past personal/family history of depression but not time since stroke. Copyright 2017. Published by Elsevier Inc.
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目的观察舒肝解郁胶囊治疗老年轻中度缺血性脑卒中后抑郁的临床疗效和对神经功能缺损的影响。方法老年轻中度缺血性脑卒中后抑郁患者84例,随机分为治疗组和对照组各42例。治疗组口服舒肝解郁胶囊0.72 g,bid;对照组口服西酞普兰片20 mg,qd。疗程均为6周。于基线及治疗第2,4,6周末分别采用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床总体印象量表(CGI)、治疗时出现的不良反应症状量表(TESS)评定疗效和不良反应,采用中国脑卒中患者临床神经功能缺损评分标准(CSS)评定对神经功能缺损的影响。结果至研究终点,治疗组和对照组有效率分别为69.0%,64.3%(P0.05);两组HAMD、HAMA评分均显著低于基线(P0.05),两组间比较差异无统计学意义(P0.05)。治疗6周末,治疗组的TESS评分显著低于对照组(P0.01),疗效指数显著高于对照组(P0.01)。治疗6周末两组CSS评分均显著低于基线,治疗组的CSS评分显著低于对照组(P0.05)。结论舒肝解郁胶囊治疗轻中度缺血性抑郁症疗效与西酞普兰相当,不良反应明显少于西酞普兰,并能促进神经功能康复。
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Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression.
[本文引用:1]
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[11] |
In this study, antidepressant-like effects of intra-cerebroventricularly administration of oxoisoaporphine derivatives in post stroke-depressive like behavior were examined through despair swimming and tail suspension models. For this aim, acute ischemic stroke was induced by bilateral common carotid arteries occlusion which significantly changed the normal behaviors of male balb/c mice. We performed stroke-induced anhedonia test as a key result of post strokedepressive like behavior by determination of sucrose consumption. Results show that some 2,3-dihydro- and oxoisoaporphine derivatives modified the abnormality in the behaviors through decreasing in the immobility time in tail suspension and despair swimming models and increasing in the swimming and climbing times in despair swimming model. We concluded that these alkaloids showed antidepressant actions and therefore can be used for treatment of post strokedepressive like behavior in acute ischemic stroke patients.
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[12] |
<正>脑血管疾病是指由各种原因导致的脑血管性疾病的总称。卒中为脑血管疾病的主要类型,包括缺血性卒中和出血性卒中。本病发病率、病死率和致残率高,给社会、家庭带来沉重的负担和痛苦。[1]随着医学的发展和人类寿命的延长,对脑血管疾病认识的提高,脑卒中(脑血管意外)本身所导致的病死率和致残率呈明显下降趋势,而卒中后抑郁(PostStroke Depression,PSD)正在一定程度上成为延缓患者神经
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[14] |
Post-stroke depression (PSD) is the most common mood disorder following a stroke, and also the main factor limiting recovery and rehabilitation in stroke patients. In addition, it may increase mortality by up to ten times. PSD occurs in 1 in 3 stroke patients and more than half of all cases are neither diagnosed nor treated. Several mechanisms, including biological, behavioral, and social factors, are involved in its pathogenesis. Symptoms usually occur within the first three months after stroke (early onset PSD), and less frequently at a later time (late onset PSD). Symptoms resemble those of other types of depression, although there are some differences: PSD patients experience more sleep disturbances, vegetative symptoms, and social withdrawal. For PSD diagnosis, we recommended vigilance and use of specific diagnostic tools such as the Patient Health Questionnaire-2 (PHQ-2). The treatments of choice are selective serotonin reuptake inhibitors (SSRI). However, there are still many unanswered questions in the treatment of PSD, such as the best time to start treatment or the effects of antidepressants on cognition and motor function, among others. Neurologists play a pivotal role in the care and management of patients recovering from stroke. They must be familiar with methods for early detection and treatment of PSD, as this can facilitate a patient's functional recovery and social reintegration, and improve quality of life for patients and their families.
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Poststroke depression has been linked to higher mortality after stroke. However, the effect of other mental health conditions on poststroke mortality has not been examined. The objective of this study was to evaluate the effect of poststroke depression and other mental health diagnoses on mortality after ischemic stroke. The authors examined a national cohort of veterans hospitalized after an ischemic stroke at any U.S. Department of Veterans Affairs (VA) medical center from 1990 to 1998. Demographic, admission, and all-cause mortality data were abstracted from VA administrative databases. Chronic conditions present at discharge and new poststroke depression and other mental health diagnoses within 3 years after the stroke were identified with ICD-9 codes. Mortality hazard ratios were modeled by using Cox regression models. A total of 51,119 patients hospitalized after an ischemic stroke who survived beyond 30 days afterward were identified; 2,405 (5%) received a diagnosis of depression, and 2,257 (4%) received another mental health diagnosis within 3 years of their stroke. Patients with poststroke depression were younger, more often white, and less likely to be alive at the end of the 3-year follow-up period. Both poststroke depression (hazard ratio=1.13, 95% CI=1.06-1.21) and other mental health diagnoses (hazard ratio=1.13, 95% CI=1.07-1.22) independently increased the hazard for death even after other chronic conditions were controlled. Despite being younger and having fewer chronic conditions, a higher 3-year mortality risk was seen in patients with poststroke depression and other mental health diagnoses after hospitalization for an ischemic stroke. The biological and psychosocial mechanisms driving this greater risk should be further explored, and the effect of depression treatment on mortality after stroke should be tested.
[本文引用:1]
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[16] |
Objectives: To examine the level of peripheral muscle resistance after cerebral ischemia. Methods: A total of 326 healthy male Sprague-Dawley rats were used in the present experiments. We used a modified method to establish peripheral muscle resistance in rat model of stroke, and qualified the recovery of motor functional deficits by behavioral measures and quantified the level of peripheral muscle resistance by electrophysiological test. Results: Neurological score started to go up from day 0, achieved its peak on day 3 (1.49 0.56) and kept at a high level within 10 days after surgery. Compared with 1 day before surgery, both the turn score in corner test and asymmetry score in cylinder test were increased significantly on day 3, day 6 and day 9 after surgery (p < 0.01). On day 6 and day 9 after surgery, the Hmax:Mmax ratio of hemiplegic side of middle cerebral artery occlusion (MCAO) rats was obviously higher than the same side in healthy rat (p < 0.01) and the ratio on the contralateral side of MCAO rats (p < 0.05). Conclusions: There is a progressive increase in peripheral muscle resistance on day 6 to day 9 after surgery in a rat model of postischemic stroke.
[本文引用:1]
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[17] |
目的研究解郁方抗抑郁作用的机理.方法采用酶联免疫检测试剂盒测定小鼠脑组织中单胺类神经递质含量;分光光度计法检测小鼠脑组织中单胺氧化酶(monoamine oxidase,MAO)活性,来研究解郁方抗抑郁作用的机制.结果解郁方Ⅰ和Ⅱ(12.00、6.00g·kg^-1)组均可显著升高小鼠脑内去甲肾上腺素、5-羟色胺、多巴胺(分别为P〈0.01,P〈0.05),解郁方Ⅰ和Ⅱ组可显著降低MAO活性(分别为P〈0.01,P〈0.05).结论解郁方可能是通过抑制MAO活性,使突触间隙的单胺类神经递质含量升高,而起到抗抑郁作用.
[本文引用:1]
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[18] |
黄蜀葵花为中国民间草药,是锦葵科秋葵属黄蜀葵[Abelmoschus manihot(L.)Medic.]的干燥花冠,已报道其具有抗抑郁活性。本文从黄蜀葵花中分离纯化得到主要黄酮类化合物,并探索其中5种化合物抗抑郁活性及其作用机制。采用D101大孔树脂柱、聚酰胺柱和Sephadex LH-20柱对黄酮类成分进行分离与纯化,经UHPLC与NMR等技术鉴定,得到8个黄酮类化合物,为杨梅素-3-O-β-D-葡糖苷(1)、棉皮素-8-O-β-D-葡糖苷酸(2,G-8-G)、棉皮素-3'-O-β-D-葡糖苷(3)、槲皮素-3'-葡糖苷(4,Q-3-G)、异槲皮苷(5,IQT)、金丝桃苷(6,HY)、杨梅黄酮(7)和槲皮素(8,QT)。采用小鼠分别灌胃化合物2、4、5、6和8(15、30、60 mg·kg~(-1))24 h后,观察悬尾实验(tail suspension test,TST)和强迫游泳实验(forced swimming test,FST),并采用Western blot技术检测小鼠海马组织中脑源性神经营养因子(BDNF)、酪氨酸受体激酶B(Trk B)和磷酸化的真核延伸因子2(p-e EF2)的表达。结果表明,化合物2和4能够显著缩短小鼠在FST和TST中的不动时间,显著增加BDNF和Trk B的表达,减少p-e EF2的表达。可见,化合物2和4可上调BDNF表达而发挥其抗抑郁活性。
[本文引用:1]
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[19] |
We investigated the question of whether an animal model of post-stroke depression in ischemic stroke can be developed by additional chronic mild stress (CMS) procedures. Behavioral and histopathological analysis was performed for examination of the depressive disorders in CMS, left middle cerebral artery occlusion (MCAO) and CMS after MCAO (MCAO+CMS) in mice. In all depressant screening tests involving open field, sucrose preference, forced swim and Morris water maze test, MCAO+CMS mice showed more significant depressive behaviors than MCAO mice. MCAO+CMS mice also showed distinct deficits in forced swim and Morris water maze test compared with CMS. In the histopathological analysis, prominent atrophic changes were seen in the striatum and midbrain of MCAO treated mice compared with CMS. MCAO+CMS mice showed a decrease of proliferative and differentiated neuronal cells in the striatum and hippocampus with dopaminergic neuronal injuries in the midbrain as compared with CMS and MCAO alone treated mice. Treatment of MCAO+CMS mice with aripiprazole resulted in reduction of all depressive behaviors examined, particularly in the Morris water maze test. Recovered dopaminergic neuronal injuries in the midbrain and enhanced neurogenesis in the hippocampus were also demonstrated. Our results suggest that CMS after ischemic stroke can lead to severe depressive-like behavior compared with CMS or MCAO alone treated mice via neurodegeneration in the primary lesion and secondary extrafocal sites and degradation of neurogenesis, and these behavioral and histopathological changes are reversed by treatment with aripiprazole. Thus adjunct therapy with an antipsychotic may exert its antidepressant effects via neuroprotection and neurogenesis in CMS-treated ischemic mice.
[本文引用:1]
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[20] |
The aim of this study was to observe the changes in the levels of learning and memory in a post-stroke depression (PSD) rat model. Forty-eight Wistar rats were randomly divided into three groups: Group A (normal group), group B (stroke group) and group C (PSD group). Each group comprised 16 rats. Three and 7 days after successful modeling, the open-field, sucrose solution consumption and forced swimming tests were performed, so as to evaluate behavioral changes in the three groups of rats. The sucrose solution consumption of the rats in group B was lower than that in group A in the tests at the two time-points, but only the difference after 7 days was statistically significant (P<0.05). The sucrose solution consumption of the rats in group C was lower than the consumption of those in groups A and B, and the differences were statistically significant (P<0.05). The open-field test results showed that the horizontal and vertical activity scores of the rats in group B were significantly lower than those of the rats in group A (P<0.05). Furthermore, the two test levels and the vertical activity scores of the rats in group C were significantly lower than those of the rats in groups A and B (P<0.05). The immobility time of the rats in the forced swimming test was higher in group B than that in group A at the two time-points, but the difference was only statistically significant after 7 days (P<0.05). The immobility time of the rats in group C was significantly higher than that in groups A and B (P<0.01). In conclusion, rats with PSD exhibited a significantly reduced memory capacity and altered behavior. The changes in the PSD rats were more severe than those in the rats in the stroke group.
[本文引用:1]
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[21] |
目的 探讨舒肝解郁胶囊对脑卒中后抑郁(PSD)患者血浆去甲肾上腺素(NE)及多巴胺(DA)水平的影响.方法 随机将60例脑卒中后抑郁患者分为治疗组与对照组各30例.两组均给予临床常规治疗(包括溶栓、抗血小板凝集、脱水、脑保护药和活血化瘀中药治疗等)和早 期康复治疗(良肢位、运动疗法、辅以偏瘫治疗仪、针灸和电刺激等),治疗组加用舒肝解郁胶囊,每次2粒(每粒0.36 g),tid,po.在治疗前1周及治疗2,4周末时抽血测血浆NE及DA含量进行比较.并对患者治疗前后汉密尔顿抑郁量表(HAMD)评分比较.结果 治疗组治疗2,4周后HAMD评分为(15.54±1.68),(6.32±1.52)分,对照组分别为(18.97±1.75)和 (15.11±1.43)分;治疗组治疗2,4周后NE分别为(0.30±0.03),(0.37±0.02) μmol·L-1,对照组分别为(0.26±0.04),(0.30±0.03) μmol·L-1;治疗组治疗2,4周后DA分别为(2.88±0.15),(3.26±0.07) μmol·L-1,对照组分别为(2.80±0.17),(2.90±0.11) μmol·L-1,治疗前两组血浆NE及DA的水平比较无明显差异,治疗4周末时,治疗组NE及DA的水平较治疗前提高(P<0.05),也较对照组增加 (P<0.05).结论 舒肝解郁胶囊可提高脑卒中后抑郁患者血浆中NE及DA的水平,从而改善抑郁状态.
[本文引用:1]
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[22] |
Depression is a polygenic and highly complex psychiatric disorder that remains a major burden on society. Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are some of the most commonly prescribed drugs worldwide. In this review, we will discuss the evidence that links serotonin and serotonin receptors to the etiology of depression and the mechanisms underlying response to antidepressant treatment. We will then revisit the role of serotonin in three distinct hypotheses that have been proposed over the last several decades to explain the pathophysiology of depression: the monoamine, neurotrophic, and neurogenic hypotheses. Finally, we will discuss how recent studies into serotonin receptors have implicated specific neural circuitry in mediating the antidepressant response, with a focus being placed on the hippocampus.
[本文引用:2]
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[23] |
Several groups have found that a significant percentage of patients with amyotrophic lateral sclerosis (ALS) have cognitive impairment. Here we investigate whether the amygdala, a temporal lobe structure, is affected by ALS. We asked patients with ALS to judge the approachability of unfamiliar faces. We showed subjects 60 faces and asked, "If you were in a strange town at dusk, would you ask... [Show full abstract]
[本文引用:1]
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[24] |
Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed.
[本文引用:1]
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[25] |
To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats.Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated.MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1β and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1β mRNA levels in the citalopram-treated group of rats.The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1β transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy.
[本文引用:1]
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