持续性植物状态猫体内多巴胺变化的实验研究

目的探讨持续性植物状态猫脑脊液、血液中多巴胺的变化及其意义。方法用高效液相色谱测定持续性植物状态的猫脑脊液、血液中多巴胺含量,并与正常对照组对比。结果持续性植物状态猫的脑脊液、血液中多巴胺含量降低。结论多巴胺的减少可能是形成持续性植物状态的重要因素之一。     

精神病患者脑立体定向术前后脑脊液中单胺类递质的变化

对16例精神病患者作了脑立体定向手术,靶点选择双扣带回、杏仁核、内囊前肢,发现术后疗效好的患者脑脊液中去甲肾上腺素含量减低,多巴胺含量升高;疗效差者脑脊液中多巴胺和去甲肾上腺素含量变化不大,提示该治疗的机理可能与中枢神经内单胺递质改变有关。     

猫脑外伤性持续性植物状态模型制作的实验研究

目的建立闭合性硬脑膜外占位性猫脑损伤后持续性植物状态(PVS)模型,探索其诊断标准。方法将水囊置放硬膜外模拟占位,然后向水囊内注入无菌水直到昏迷,并对动物模型进行评估。结果手术一个月后,有12只猫处于植物状态,动物模型的临床表现、体征等与PVS病人相近。结论本实验制作的PVS动物模型与临床病人相似,是一种比较理想的PVS动物模型。     

迁算性植物状态患者血清中多巴胺含量的临床意义

目的：探讨迁延性植物状态患者血清中多巴胺的变化及其临床意义。方法：用高效液相色谱测定长期昏迷的病人,并与正常对照组对比。结果：迁延性植物状态患者的血清中多巴胺显著降低。结论：多巴胺的减少可能是形成迁延性植物状态的重要因素之一。     

迁延性植物状态患者血清中多巴胺含量的临床意义

目的：探讨迁延性植物状态患者血清中多巴胺的变化及其临床意义。方法：用高效液相色谱测定长期昏迷的病人，并与正常对照组对比。结果：迁延性植物状态患者的血清中多巴胺显著降低。结论：多巴胺的减少可能是形成迁延性植物状态的重要因素之一。     

偏侧猴帕金森病模型的脑深部电刺激研究

目的 探讨丘脑底核脑深部电刺激(STN DBS)对纹状体多巴胺代谢的影响.方法 2只偏侧帕金森病(PD)模型猴,在电极植入术前及电刺激后1、3个月分别行单光子放射计算机断层扫描(SPECT)测定脑内多巴胺转运体(DAT)及多巴胺D2受体(D2R)的含量;利用高效液相色谱分析(HPLE-ECD)检测脑脊液中多巴胺及其代谢产物的含量和变化.结果 偏侧PD模型猴在深部脑刺激下症状明显缓解,SPECT显示在有效刺激后纹状体区DAT特异性摄取率增高,D2R特异性摄取率下降.脑脊液中多巴胺及其代谢产物的含量与术前相比无明显差异.结论 STN DBS可有效改善偏侧PD模型猴的症状.SPECT提示有效电刺激STN提高了纹状体区多巴胺代谢活性.     

双侧杏仁核破坏术后精神分裂症患者脑脊液单胺神经递质的变化

本文报道12例慢性精神分裂症经杏仁核破坏术后脑脊液单胺神经递质的变化,发现患者高香草酸增多,术后减少,符合多巴胺假说。本文并就脑脊液单胺神经递质的含量及作用进行了讨论。     

舒必利治疗精神分裂症患者脑脊液HVA含量的对照研究

为了探讨精神分裂症患治疗期间多巴胺的变化，我们选择舒必利治疗组20例，非舒必利治疗组10例作为病例组；15例非精神病患作为对照组；检测脑脊液中多巴胺代谢产物高香草酸的含量；结果显示两组无显性差异。精神分裂症患治疗后舒必利组高香草酸含量升高，非舒必利组则降低，进一步分析显示舒必利治疗组非显效较显效治疗后高香草酸显升高。提示机体对药物阻滞多巴胺受体后代偿反应的强弱与疗效有一定关系。     

猫持续性植物状态动物模型的建立

目的：建立猫持续性植物状态(PVS)动物模型。方法：16只成年健康家猫随机分为2组．实验组12只右颞开颅，抬起颞叶．暴露中脑及动眼神经，基本平动眼神经水平，用宽8mm、厚1mm金属毁损器横行插入中脑，深度11mm。术后饲养一个月处死动物。结果：实验组12只动物中1只因基底动脉损伤、1只因胃管内返流液误吸死亡，余10只动物均达PVS标准。结论：中脑网状结构毁损法可使猫达到PVS。     

大剂量维生素C治疗猫急性颅脑伤的实验研究——几种神经肽含量的变化

以自由落体法致猫脑挫裂伤,伤后静脉滴注维生素C 200mg/kg,通过测定血浆和脑脊液中AVP、Dyn—A、NT和SS的含量以及颅内压和脑含水量的变化,评估大剂量维生素C对急性颅脑伤的治疗效果。结果显示颅脑伤早期应用大剂量维生素C,能有效地遏制血浆和脑脊液中神经肽含量的升高,减轻脑水肿,降低颅内压。     

HPLC法检测PVS患者脑脊液中氨基酸类神经递质

目的 探讨HPLC法检测脑脊液中氨基酸类物质的方法,观察PVS患者脑脊液中氨基酸类神经递质的变化。方法28例PVS患者与15例对照病人分別采集脑脊液,经过预处理后运用OPA柱前衍生化法分別检测谷氨酸(glutamjc acid,Glu)、天冬氨酸(aspanic acid,Asp)、丙氨酸(alaninc,Ala)、甘氨酸(glycinc,Gly)。结果 本实验条件下,4种氨基酸在25 min内得以较好分离。峰面积与氨基酸浓度的线性关系良好。PVS组4种递质水平均高于对照组,其中Ala的差异有统计学意义(P<0.05)。结论 HPLC法检测脑脊液中氨基酸类物质方法简便易行,准确度高。PVS患者脑脊液中Ala水平显著升高。     

Decreased cerebrospinal fluid levels of beta-phenylethylamine in patients with Rett syndrome

To clarify the mechanism of brain impairment in Rett syndrome, we measured the cerebrospinal fluid levels of beta-phenylethylamine (PEA) in 17 patients with Rett syndrome. Findings were compared with those obtained in age-matched controls and diseased controls. The cerebrospinal fluid level of PEA was significantly lower in patients with Rett syndrome than in the controls (31% of control values). The alteration in the cerebrospinal fluid level of PEA may reflect dopamine system impairment in Rett syndrome.     

6-Hydroxydopamine-induced turning behaviour in the rat: the significance of acetylcholinesterase in cerebrospinal fluid

In the substantia nigra, acetylcholinesterase may have a novel function related not to cholinergic transmission, but to the homeostasis of dopaminergic nigrostriatal neurones. The initial aim of this study was thus to see whether, in the rat, release of the enzyme into cerebrospinal fluid would reflect turning behaviour following unilateral 6-hydroxydopamine lesions of varying severity. It was found that acetylcholinesterase levels, lower than those in the cerebrospinal fluid of control rats, were accompanied by marginal circling behaviour and a small loss of striatal dopamine: on the other hand, elevated acetylcholinesterase activity was observed in the cerebrospinal fluid of rats displaying vigorous turning behaviour and with large depletion of striatal dopamine. It has already been demonstrated that exogenous acetylcholinesterase, applied locally to nigral neurones, has both electrophysiological and behavioural effects reminiscent of dopamine agonists. Hence it is possible that exogenous acetylcholinesterase could modify turning behaviour resulting from unilateral striatal dopamine depletion. Purified acetylcholinesterase, administered by cisternal puncture, attenuated circling behaviour for up to 7 days. The possible mechanisms are discussed by which endogenous acetylcholinesterase in cerebrospinal fluid could serve as an index of dopamine depletion in the nigrostriatal pathway and how exogenous enzymes might alleviate the accompanying motor dysfunction.     

Effect of Yishen Qiqiao Fang on dopamine content in serum and cerebrospinal fluid of patients in persistent vegetative statec

BACKGROUND: It has been demonstrated that the attack of persistent vegetative state is associated with the damaged neuron, which produces dopamine, and nervous pathway, the reduce of dopamine or malfunction of dopamine. OBJECTIVE: To observe the effect of self-made traditional Chinese medicine (TCM) Yishen Qiqiao Fang, which has the functions of supplementing qi and nourishing blood, resolving phlegm by promoting blood circulation, restoring consciousness and inducing resuscitation, on the contents of dopamine in serum and cerebrospinal fluid of patients in persistent vegetative state. DESIGN: An open randomized controlled clinical trial. SETTINGS: Nanjing University of Traditional Chinese Medicine, Nanjing Zijin Hospital. PARTICIPANTS: Thirty-eight inpatients of persistent vegetative state were selected from the Department of Neurology, Nanjing Zijin Hospital from August 2005 to November 2006. The patients were diagnosed according to the diagnostic standards set by the summary of a meeting for specialists in Nanjing. Informed contents were obtained from their relatives. According to the order of admission, the enrolled patients were divided into control group (n =20) and TCM treated group (n =20). METHODS: In the control group, the patients were treated with routine treatments for the symptoms. In the TCM treated group, the patients were treated with Yishen Qiqiao Fang besides the same treatments in the control group. TCM dispensing granules: each bag of mongolian milkvetch root, Chinese angelica and peach seed equaled to 10 g crude drug respectively; each bag of grassleaf sweetflag rhizome and dahurian angelica root equaled to 6 g crude drug respectively; Musk 0.05 g. The daily dosage for adults: 4 bags of mongolian milkvetch root, 2 bags of Chinese angelica, 0.05 g musk, 1 bag of peach seed, 2 bags of grassleaf sweetflag rhizome and 2 bags of dahurian angelica root, which should be given though nasal feeding or gastrostogavage before breakfast and supper every day, the course lasted for 2 months. The contents of dopamine in serum and cerebrospinal fluid were determined with enzyme immunoassay analyzer before and after treatment in both groups. MAIN OUTCOME MEASURES: Contents of dopamine in serum and cerebrospinal fluid before and after treatment in both groups. RESULTS: Totally 38 patients of persistent vegetative state were enrolled, 33 of them were involved in the final analysis of results, and the other 5 missed. The contents of dopamine in serum and cerebrospinal fluid had no obvious differences between the two groups both before and after treatment (P > 0.05). In the control group, the contents of dopamine in serum and cerebrospinal fluid had no obvious differences before and after treatment (P > 0.05). In the TCM treated group, the contents of dopamine in serum and cerebrospinal fluid after treatment were obviously higher than those before treatment (t =2.174, 2.485, P < 0.05). CONCLUSION: Yishen Qiqiao Fang can significantly increase the contents of dopamine in serum and cerebrospinal fluid of patients in persistent vegetative state, which may be one of the mechanisms for ameliorating persistent vegetative state.     

血管周围间隙与Alzheimer’s病相关性的研究

Alzheimer’s病(AD)是一种渐进性神经系统变性病。近年来发现小血管病在AD患者中广泛存在并参与AD的病理过程。血管周围间隙(PVS)是蛛网膜下腔小动静脉穿过脑实质时形成的围绕在血管周围的腔隙,为脑小血管病的影像学表现形式之一。本文对PVS中CSF-组织间液循环通路、PVS内β样淀粉蛋白清除机制以及PVS扩张的形成因素进行阐述,探讨PVS扩张对AD的发展及认知功能的影响。PVS与AD相关性的研究可能对AD药物治疗的研发提供一定指导意义。     

Evidence for a ‘Paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space

The protein tracer, horseradish peroxidase (HRP), was infused into the lateral cerebral ventricles or subarachnoid space of anesthetized cats and dogs after insertion of a cisternal cannula to permit drainage of cerebrospinal fluid (CSF) and tracer solution. The intracerebral distribution of the tracer was then determined by light microscopy of serial brain sections after postinfusion intervals of 4 min-2 h. For the localization of HRP, sections were incubated with diaminobenzidine (DAB) or the much more sensitive chromogen, tetramethylbenzidine (TMB). The TMB reaction showed a consistent 'paravascular' distribution of tracer reaction product, within the perivascular spaces (PVS) around large penetrating vessels and in the basal laminae around capillaries, far beyond the termination of the PVS. After infusion of HRP over 4 min, arterioles were surrounded by the tracer, but capillaries and venules were usually less densely demarcated; by 6 min, however, the intraparenchymal microvasculature was outlined in toto throughout the forebrain and brainstem. Electron microscopy of sections incubated in DAB after 10 or 20 min HRP circulation confirmed the paravascular location of the reaction product, which was also dispersed throughout the extracellular spaces (ECS) of the adjacent parenchyma. Our results demonstrate that solutes in the CSF have access to the ECS throughout the neuraxis within minutes via fluid pathways paralleling the intraparenchymal vasculature. The rapid paravascular influx of HRP could be prevented by stopping or diminishing the pulsations of the cerebral arteries by aortic occlusion or by partial ligation of the brachiocephalic artery. The exchange of solutes between the CSF and the cerebral ECS has generally been attributed to diffusion, however, HRP enters the neuraxis along the intraparenchymal microvasculature far more rapidly than can be explained on this basis. This apparent convective tracer influx may be facilitated by transmission of the pulsations of the cerebral arteries to the microvasculature. We postulate that a fluid circulation through the CNS occurs via paravascular pathways.     

Dopamine metabolism in the cerebrospinal fluid of drug-free schizophrenic patients with and without cortical atrophy

Cortical atrophy measured with computed tomography was observed in ten of 53 schizophrenic patients. Levels of homovanillic acid, dihydroxyphenyl acetic acid (DOPAC), conjugated DOPAC, and dopamine sulfate (DASO4) were measured in the cerebrospinal fluid of these patients during a drug-free evaluation. Patients with cortical atrophy had lower cerebrospinal fluid levels of homovanillic acid, DOPAC, and conjugated DOPAC but higher DASO4 levels. Combined measures of dopamine utilization were significantly lower in patients with cortical atrophy. We did not find significant clinical or demographic differences between the patients with and without cortical atrophy. Patients without brain atrophy who had dopamine utilization above the mean showed more psychotic symptoms and shorter duration of illness, while those with dopamine below the mean had more negative symptoms. We propose that both state- and trait-dependent variables affect dopamine turnover.     

CSF sulfoconjugated catecholamines in man: Their relationship with plasma catecholamines

Summary Simultaneous plasma and cerebrospinal free and sulfoconjugated norepinephrine, epinephrine, dopamine and homovanillic acid determinations in 38 patients with various neurological disorders have shown consistently lower concentrations of dopamine sulfate, norepinephrine sulfate, and epinephrine sulfate in the cerebrospinal fluid than in plasma. An approximately three fold increase of plasma dopamine sulfate concentrations following banana ingestion did not result in increased dopamine sulfate concentrations in cerebrospinal fluid. There were positive correlations between plasma and cerebrospinal fluid concentrations of free norepinephrine and epinephrine as well as norepinephrine sulfate, dopamine sulfate and free homovanillic acid. Cerebrospinal fluid and plasma are apparently separated by the blood-brain barrier impermeable to catecholamine sulfates from the blood. Some other data and the observed positive correlation between cerebrospinal fluid and plasma dopamine and norepinephrine sulfates suggests however that catecholamine sulfates may pass from cerebrospinal fluid to the blood and reflect events in the brain.This work was supported by a grant from the Medical Research Council of Canada to a multidisciplinary group in hypertension.We wish to thank for efficient nursing help Mrs.M. Vautour R. N.,F. Salvail R. N.,M. A. Boutin R. N., andC. Doyon R. N., for laboratory work Mrs.Dominique Chevalier andCarmen Savard, for statistical analysis Dr.Michel Bourque and for secretarial help Mrs.Sylvie Ouellet-Collon.