The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Clinical Observation on Acupuncture Treatment of Cerebrovascular Dementia——A Report of 32 Cases

Cerebrovascular dementia is a common disease in the middle-aged and old people. Its incidence makes up about 10-20% of all kinds of dementia. It is mainly caused by general degeneration of the brain function resulted from cerebral arteriosclerosis and cerebral infarction. The author has treated 32 cases of cerebrovascular dementia with acupuncture in the recent years with satisfactory therapeutic results. A report follows.

Clinical Study on Treatment of Senile Vascular Dementia by Acupuncture

63 patients with senile vascular dementia were randomly divided into the treatment group (treated by acupuncture) and the control group (treated with piracetam). The authors observed the changes in the score of Hasegawa's dementia scale (HDS), p300, rheoencephalogram, topographic EEG, superoxide dismutase (SOD) activity in erythrocytes, and lipid peroxide (LPO) level in plasma before and after treatment. The statistical data showed that the total effective rate in the treatment group (80.6%) was significantly higher than that in the control group (25%), and the differences in the observed indexes before and after treatment were significant (P 0.05), indicating that the acupuncture treatment was superior in immediate therapeutic effect on senile vascular dementia to drug treatment.

CLINICAL STUDY ON TREATMENT OF VASCULAR DEMENTIA WITH ELECTROACUPUNCTURE OF "SISHENCHONG

Aim: To observe the therapeutic effect of electroacupuncture (EA) in the treatment of vascular dementia. Methods: A total of 46 cases of vascular dementia (VD) patients were divided into 3 classes according to the scores of the revised Hasegawa dementia scale (HDS), and then randomized into EA group (n=23) and medication (Nimodipine) group (n=23). The acupoints used were "Zhisanzhen" [Shenting (GV 24) and bilateral Benshen (GB 13)] and Sishenchong (EX HN 1) etc.. Scores of HDS, ability of daily life (ADL), neurofunctional defect and main symptoms were used as the indexes for assessing the therapeutic effect. Results: Following treatment, scores of HDS and ADL of two groups increased significantly, while those of neurofunctional defect and main symptoms decreased evidently (P<0.01), and the therapeutic effect of EA was obviously superior to that of medication (P<0.01). Conclusion: EA of "Zhisanzhen" and Sishenchong (EX HN 1) is a good approach for treatment of VD.

A COMPARATIVE STUDY ON THE TREATMENT OF VASCULAR DEMENTIA BY PUNCTURING BAIHUI (GV20), SHUIGOU (GV26) AND SHENMEN (HT7)

Objective: To observe the relative specialty of the therapeutic effect of acupuncture of Baihui (百会 GV 20), Shuigou (水沟 GV 26) a nd Shenmen (神门 HT 7) in the treatment of vascular dementia (VD) patients. Methods: F ifty VD patients were randomly divided into routine treatment group (control gro up), Baihui (GV 20) group (GV 20 group), Shuigou (GV 26) group (GV 26 gr oup), Shenmen (HT 7) group (HT 7 group) a nd GV 20+GV 26+HT 7 group (joint treatment group), with 10 cases in ea ch group. In control group, acupoints used were Jianyu (肩NFDA1 LI 15), Quchi (曲池 L I 11), Waiguan (外关 TE 5), etc. (which were also used in the other four groups) on the paralyzed side. The treatment was conducted once a day except weekends, 20 session s all together. Clinical Dementia Rating Scale (CDR), Mini-Mental State Examin at ion (MMSE) test, Blessed Dementia Rating Scale (BDR) and Clinical Neurological D eficit Rating (CNDR) were used to assess the patients’ intelligence state befor e and after acupuncture treatment. Results: After acupuncture tr eatment, the VD patients’ intelligence in all the five groups was improved at different degrees . Additional acupuncture of each of GV 20, GV 26 and HT 7 had a remarkable e ffec t in improving the VD patients’ fluid intelligence, and could obviously promote their abilities of temporal orientation, spatial orientation and figure drawing ; and additional joint acupuncture of the three acupoints could improve their co gnitive and non-cognitive functions, such as reducing the severity of dementia , raising the temporal orientation, spatial orientation, calculation, short-term m emory and figure drawing abilities, and improving their activities of daily livi ng and personality. Besides, acupuncture of GV 20 could improve the abilities of calculation and short term memory, and correct the personality change of VD pat ients, while acupuncture of GV 26 could improve the abilities of naming and sh or t-term memory. Conclusion: Acupuncture of GV 20, GV 26 and HT 7 all had a certai n therapeutic effect in improving VD; the therapeutic effects of acupuncture of GV 20 and GV 26 were better than that of acupuncture of HT 7; and the effica cy of the three points used in combination was the best.

经颅重复针刺对血管性痴呆模型大鼠认知功能及海马突触超微结构的影响

目的 观察经颅重复针刺对血管性痴呆(vascular dementia, VaD)大鼠认知功能及海马CA1区突触素(synaptophysin, SYN)、微管相关蛋白-2(microtubule associated protein-2, MAP-2)表达的影响。方法 将56只SD大鼠随机分为空白组(14只)和造模组(42只)。造模组建立VaD模型,将造模成功大鼠随机分为模型组(14只)、常规针刺组(14只)和经颅重复针刺刺激(repetitive transcranial acupuncture stimulation, rTAS)组(14只)。造模成功后第2天,rTAS组采用经颅重复针刺;常规针刺组仅给予常规针刺手法;模型组与空白组给予以同等条件抓取及固定,不予针刺。采用水迷宫评价大鼠学习记忆能力,采用旷场实验评价大鼠探索行为和自主活动能力,免疫印迹法检测海马CA1区SYP、MAP-2蛋白表达水平,透射电镜观察海马组织中突触超微结构。结果与空白组比较,模型组逃避潜伏时间明显增加(P<0.05),穿越平台次数明显减少(P<0.05);与模型组比较,常规针刺组与rTAS组逃避潜伏时间明显减少(P<0.05),穿越平台次数明显增加(P<0.05);与常规针刺组比较,rTAS组逃避潜伏时间与穿越平台次数改变不明显(P>0.05)。与空白组比较,模型组穿越格子数与后肢站立数明显减少(P<0.05);与模型组比较,常规针刺组与rTAS组穿越格子数与后肢站立数明显增加(P<0.05);与常规针刺组比较,rTAS组穿越格子数与后肢站立数明显增加(P<0.05)。与空白组比较,模型组SYP、MAP-2表达水平显著降低(P<0.05);与模型组比较,常规针刺组与rTAS组SYP、MAP-2表达水平显著增高(P<0.05);与常规针刺组比较,rTAS组SYP、MAP-2表达水平显著增高(P<0.05)。电镜下,模型组突触结构欠清晰,突触间隙模糊不清,突触小泡较少,突触前致密物质减少,胞浆内细胞器稀疏,线粒体变形肿大明显;而rTAS组突触结构较完整,突触间隙、突触前后膜分界清晰,突触前膜内囊泡较多,突触后膜均匀增厚,周边线粒体丰富、结构完整。结论 经颅重复针刺较常规针刺可能通过调控SYP、MAP-2表达,更有效促进突触再生,改善突触可塑性,修复受损神经元,从而改善认知功能。

理性情绪疗法联合中医情志干预对血管性痴呆患者焦虑抑郁症状的影响

目的观察理性情绪疗法联合中医情志干预对血管性痴呆患者焦虑抑郁症状的影响。方法将80例血管性痴呆患者按照随机数字表法分为2组,对照组40例予常规基础干预,观察组40例在对照组干预基础上采用理性情绪疗法联合中医情志干预,2组均干预4周。比较2组干预前后简易智能状态检查表(MMSE)、日常生活能力量表(ADL)、老年痴呆患者生活质量量表(QOL-AD)评分、汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分变化;比较2组干预满意度。结果2组干预后MMSE评分均较本组干预前升高(P<0.05),干预后观察组高于对照组(P<0.05)。2组干预后ADL评分均较本组干预前降低(P<0.05),QOL-AD评分均较本组干预前升高(P<0.05);干预后观察组ADL评分低于对照组(P<0.05),QOL-AD评分高于对照组(P<0.05)。2组干预后HAMD评分、HAMA评分均较本组干预前降低(P<0.05),干预后观察组HAMD评分、HAMA评分均低于对照组(P<0.05)。观察组各项满意度均高于对照组(P<0.05)。结论理性情绪疗法联合中医情志干预,能有效改善血管性痴呆患者心理状态和认知功能,提高其日常生活能力、生活质量和干预满意度。

基于《灵枢·本神》探讨从“心-脾-肾”轴论治血管性痴呆

血管性痴呆的发生发展,可责之于心、脾、肾三脏功能失调并相互干扰所诱发的神失所养、气血瘀滞、痰蒙清窍、阳亢风动等一系列病理变化;通过古方分析,探究调气活血、补益养神、祛痰开窍、平熄肝风等从“心-脾-肾”轴论治血管性痴呆的思路。

血管性痴呆的研究进展

血管性痴呆(VaD)是因脑卒中后大脑血液供应减少引起脑细胞缺血缺氧,从而出现严重认知功能障碍的疾病。VaD是一种可以预防的病症,但因其病因复杂、诊断困难的特点,使得其在神经科学和老年医学领域中占据较高的地位。目前在治疗上,现代医学主要采取口服多奈哌齐等药物控制血管性危险因素以及改善认知功能等(非)药物治疗方案;中医学则通过望闻问切达到对疾病的整体了解,并根据辨证论治对不同个体采取不同的中医特色治疗措施。文章对VaD发病相关因素、发病机制和中西医治疗方案进行综述。

Moxibustion therapy improving delayed memory deficits via promoting neurogenesis and angiogenesis of hippocampus in a vascular dementia rat model

Objective:To investigate the alteration of delayed memory and its relationship with neurogenesis and angiogenesis in vascular dementia(VD)rats after moxibustion therapy.Methods:Two hundred adult male SPF Wistar rats were chosen for the experiment.Thirty-six rats were randomly selected as the sham operation group.Except for rats in the sham operation group(n=36),the others were made into VD models by bilateral comm on carotid arteries occlusi on(BCCAo).After modeli ng,the 108 survived rats were ran domly divided into 3 groups:a model group,a neural stem cells(NSCs)plus endothelial progenitor cells(EPCs)moxibustion group and a NSCs moxibustion group.Co-transplanted implant was transplanted into the rats in the NSCs plus EPCs moxibustion group,and the rats in the NSCs moxibustion group were transplanted by NSCs only.The NSCs plus EPCs moxibustion group and the NSCs moxibustion group received suspended moxibustion therapy at Baihui(GV 20),Dazhui(GV 14)and Shenting(GV 24),(each group was divided into 3 subgroups by the treatment course as 1,2 and 3 courses).Every group was measured by Morris water maze to evaluate its delayed memory after 3 treatment courses and the rat's brain was taken out after perfusion of 4%paraformaldehyde one day after 1,2 and 3 treatment courses,respectively.Marker protein expression was detected by laser con focal microscope to an a lyze the effect on neuroge nesis and an gioge nesis.Results:VD rats showed delayed memory in Morris water maze test 3 d after ischemic injury.After 3 courses of moxibustion therapy,VD-induced delayed memory deficits were improved in the NSCs plus EPCs moxibustion group and the NSCs moxibustion group.The expressions of nestin,doublecortin(DCX)and CD34 increased significantly in the two moxibusiton groups after every treatment course(all P<0.05),which might contribute to the neurogenesis and angiogenesis in hippocampus.In addition,compared with the rats in the NSCs moxibustion group,the expressions of nestin,DCX and CD34 increased significantly in the NSCs plus EPCs moxibustion group(P<0.05).Conclusion:Moxibustion can reverse VD-induced delayed memory deficits,which may be related to the promotion of neurogenesis and angiogenesis.

温胆汤合半夏泻心汤治疗轻中度血管性痴呆临床观察

目的:观察温胆汤合半夏泻心汤治疗轻中度血管性痴呆患者的临床疗效。方法:选取轻中度血管性痴呆患者70例,随机分为两组各35例。两组患者均予基础治疗,对照组予盐酸多奈哌齐片治疗,治疗组予温胆汤合半夏泻心汤治疗,1个月为1个疗程,治疗3个疗程。比较两组患者的临床疗效以及治疗前后简易智能状态检查量表(MMSE)、日常生活能力量表(ADL)评分、中医证候积分及血清MMP水平。结果:治疗组临床总有效率88.57%,明显高于对照组的71.43%(P﹤0.05);治疗后两组MMSE评分均升高(P﹤0.05),且治疗组高于对照组(P﹤0.05);两组ADL评分、中医证候积分及血清MMP-2、MMP-9水平均降低(P﹤0.05),且治疗组降低程度较对照组更明显(P﹤0.05)。结论:温胆汤合半夏泻心汤治疗轻中度血管性痴呆患者疗效明显,可有效改善患者的认知功能和日常生活能力。

益气复元合剂治疗非痴呆型血管性认知障碍的临床研究

[目的]探讨益气复元合剂对非痴呆型血管性认知障碍(Non dementia vascular cognition impairment,VCIND)患者认知及执行能力及P300的影响,并且与丁苯酞软胶囊相对比,比较两组疗效的差异。[方法]采用简单随机数字表法将60例VCIND患者随机分治疗组和对照组各30例。所有患者均予以抗血小板聚集、调控血压、血糖、降脂、稳斑等基础治疗;在上述治疗基础上,治疗组加用益气复元合剂50ml口服,tid;对照组加用丁苯酞软胶囊口服0.2gtid,疗程为3个月;评估两组患者治疗前后MoCA和MMSE评分,检测P300潜伏期及波幅的改变,同时检测所有患者治疗前后肝肾功能、血常规、凝血功能等指标,记录不良反应。[结果]治疗前两组患者的MMSE、MoCA、P300波幅及潜伏期无明显差异(P>0.05)。治疗后两组患者MMSE、MoCA评分均升高,与治疗前相比有统计学意义(P<0.05),组间相比无明显差异(P>0.05);治疗后两组患者的P300潜伏期缩短、波幅增高,与治疗前相比有明显差异(P<0.05),且治疗组优于对照组(P<0.05)。[结论]益气复元合剂治疗能够改善VCIND患者的认知力和执行力,与丁苯酞具有相似的疗效,但在改善P300潜伏期及波幅方具有潜在的优势(P<0.05)。

黄蒲通窍胶囊对血管性痴呆大鼠神经细胞凋亡Fas/FasL蛋白表达的影响

目的探讨黄蒲通窍胶囊对血管性痴呆大鼠神经细胞凋亡Fas/FasL蛋白表达的影响机制。方法制作线栓法大脑中动脉栓塞所致的血管性痴呆大鼠模型,观察各组大鼠神经细胞凋亡Fas/FasL蛋白表达的变化。结果4周后模型组大鼠皮层(额顶叶皮质)及海马CA1区神经细胞内有大量的Fas、FasL蛋白表达,中药组的阳性细胞数明显降低,有显著性差异(P<0.01)。结论黄蒲通窍胶囊可能通过Fas信号路径抑制神经细胞凋亡而起到改善记忆和认知功能的作用。

原络配穴为主治疗血管性痴呆疗效观察

目的 :观察针刺为主治疗血管性痴呆的临床疗效。方法 :以原络配穴为主联合都可喜治疗为观察组 ,设单纯都可喜为对照组 ,观察 6 6例血管性痴呆 (VD)患者治疗前后临床症状及MMSE、HDS R、ADL变化。结果 :观察组能够提高血管性痴呆患者MMSE、HDS R的评分 ,改善ADL评分 ,临床总有效率为 85 3% ,与对照组比较差异有显著性意义 (P <0 0 5 )。结论 :原络配穴为主联合都可喜可改善VD患者的智能水平 ,恢复生活自理能力 ,近期疗效优于单纯都可喜治疗。

电针治疗血管性痴呆近期疗效分析

将46例血管性痴呆(VD)患者配对随机分为电针组和对照组(针刺组)。观察治疗前后HDS、FAQ、CCSE的评分值,SOD、LPO、GSH—Px、血脂和NO等含量以及EEG、TCD等的变化。结果治疗后电针组有效率为52.2％,总有效率为87.0％,显著高于对照组的13.0％和47.8％(P<0.01);上述各项指标均有显著性变化(P<0.05～0.01),而对照组变化不明显(P>0.05)。提示电针治疗VD近期疗效优于对照组,对VD的近期智能康复有显著作用。

电针与氢化麦角碱对血管性痴呆大鼠脑乙酰胆碱酯酶的作用

目的 探讨电针对血管性痴呆 (VD)大鼠的学习记忆行为及乙酰胆碱酯酶 (ACh E)的影响。方法 将制成肾性高血压 (RHR)后再造脑反复缺血拟 VD的大鼠 30只 ,随机分为模型组、电针组和药物组 (用氢化麦角碱 ,DHET)各 1 0只 ,共治疗 2 8d。治疗后均以水迷宫检测学习记忆行为情况 ,并检测脑 Ach E含量。结果 电针组、药物组水迷宫潜伏期明显短于模型组 (P<0 .0 5～ P<0 .0 0 5) ,电针组短于药物组 (P<0 .0 5～ P<0 .0 0 5)。在海马、纹状体 ,电针组和药物组的 Ach E含量显著高于模型组 ,而电针组又高于药物组 (P<0 .0 5)。结论 电针能改善 VD大鼠学习记忆能力 ,提高脑 Ach E含量并使之重新分布 ,其作用优于 DHET。

参龙汤治疗血管性痴呆的临床研究

目的:观察参龙汤治疗血管性痴呆(VD)的临床疗效。方法:参照WHO公布的美国精神病学会VD诊断标准(DSM- IV),入选36例(72例次)VD患者,随机双盲给药,安慰剂对照,自身前后交叉试验为研究方法,选择简易智能量表(MMSE)、Blessed行为量表(BBS)于疗程前后统计分值变化进行疗效评估。结果:参龙汤治疗VD患者36例,显效5例(13. 89% ),有效22例(61. 11% ),无效9例(25% ),总有效率75%。该药可以提高VD患者不同痴呆量表的积分,对VD患者的认知障碍有明显改善作用;还可改善VD患者的临床症状,改善其日常生活自理能力和神经功能缺损程度;对VD患者血脂、血液黏滞度及脑葡萄糖代谢亦有一定改善作用。其效应明显优于安慰剂(P<0. 001)。结论:肾虚精亏,气虚血瘀是VD的主要病机,补肾填精,益气活血法是治疗本病的重要方法,参龙汤对VD确有一定疗效,安全可靠。

头穴久留针治疗血管性痴呆的随机对照研究

目的 :观察头穴不同留针时间对血管性痴呆 (VD)的作用差异。方法 :将 60例VD患者随机分为 3组 :头穴久留针组(A组 ) ,应用头针穴位长时间留针治疗 (留针 1 0h) ;头穴电针组 (B组 ) ,应用常规头针穴位电刺激治疗 (留针 30min) ;药物治疗组 (C组 ) ,口服脑通片 (1 0mg,每日 3次 )。应用长谷川痴呆修改量表 (HDS)、简易智力状态检查量表 (MMSE)和社会功能活动调查表 (FAQ)于治疗前后分别评分 ,同时检测治疗前后血清T3 、T4、FT3 指标。结果 :治疗后 3组HDS、MMSE、FAQ评分改变差异均有非常显著性意义 (P <0 0 1 ) ;A组与B组上述评分较C组差异有显著性意义(P <0 0 5) ,A组与B组间比较差异无显著性意义 (P >0 0 5) ;治疗后各组血清T3 、FT3 水平升高 ,其变化均有显著性意义 (P <0 0 5) ,但 3组间比较差异无显著性意义 (P >0 0 5)。结论 :头穴留针 1 0h与留针 30min均可促进VD患者智能。

针刺对拟血管性痴呆大鼠脑内NO、NOS及血液流变学影响的实验研究

目的:建立拟血管性痴呆(VD)的动物模型,探讨针刺对VD大鼠模型的学习记忆行为、脑内NO含量、NOS活性及VD大鼠血液流变学的影响。方法:选用纯系健康雄性Wistar大鼠36只,随机分成假手术组、模型组、针刺组和西药对照组,采用2-血管阻断法(2-VO)制作VD大鼠模型。在大鼠“百会”“大椎”穴行针刺治疗。检测VD大鼠穿梭箱实验成绩,比色法检测脑组织NO含量、NOS活性,并检测VD大鼠的全血粘度、血浆粘度、红细胞压积及纤维蛋白原浓度。结果:数据经统计学处理表明,针刺“百会”“大椎”穴可明显减少模型大鼠在穿梭箱实验中的电击次数和电击时间(P<0.01);降低脑组织内NO的含量及NOS活性(P<0.05);可使VD大鼠的全血粘度、血浆粘度、红细胞压积及纤维蛋白原浓度降低(P<0.05,0.01)。结论:针刺能改善VD大鼠的学习记忆能力,降低脑组织内NO的含量及NOS活性,改善VD大鼠的血液流变学状态,从而改善大脑的血液供应,促进智能的恢复。

参龙汤治疗老年血管性痴呆的临床研究

目的观察参龙汤治疗老年血管性痴呆(VD)的临床疗效。方法参照WHO公布的美国精神病学会VD诊断标准(DSM-IV),采用随机对照双盲法,将68例符合条件的老年VD患者分为治疗组和对照组。治疗组36例,口服中药参龙汤(主要成分为:人参6g、何首乌15g、仙灵脾12g、地龙15g、川芎10g、益智仁15g、生神曲10g等)3个月;对照组32例,服用脑复康3个月。选择简易智能量表(MMSE)、Blessed行为量表(BBS)于治疗前后进行比较,评估疗效。结果参龙汤、脑复康均可改善老年VD患者的认知功能、行为能力,对痴呆治疗的总体疗效相近;治疗后两组痴呆患者定向能力和短时记忆能力的改善较治疗前均有显著的提高(P<0.01),参龙汤可明显改善老年痴呆患者生活能力,与治疗前比较有显著性差异(P<0.01),而脑复康组治疗后与治疗前比较未能显示出有显著性差异,说明参龙汤在改善痴呆患者生活能力方面要优于脑复康。结论参龙汤对老年VD确有一定疗效,可改善老年血管性痴呆患者的智力和生活能力。