松果菊苷对脑缺血大鼠双侧脑组织中单胺类神经递质的影响

目的:研究对比大鼠脑缺血后缺血区和非缺血区单胺类神经递质及其代谢产物的变化,考察松果菊苷(ECH)对大鼠脑缺血后双侧脑组织中单胺类神经递质及其代谢产物的影响。方法:SD大鼠随机分为假手术对照组、模型组、ECH高、低剂量组(30,15 mg.kg-1.d-1)和川芎嗪组(CXQ,30 mg.kg-1.d-1)。各组大鼠腹腔注射相应的药物或生理盐水,qd,连续7 d。于给药d 3,进行大脑双侧脑组织纹状体埋置探针套管,末次给药1 h后,制作大鼠局灶性脑缺血模型(MCAO),造模后立刻进行微透析,将透析液注入高效液相-电化学检测器(HPLC-ECD),测定各组缺血后300 min内纹状体细胞外液中去甲肾上腺素(NE)、多巴胺(DA)、3,4二羟苯乙酸(DOPAC)、5-羟色胺(5-HT)和5-羟基吲哚乙酸(5-HIAA)的含量。结果:与假手术组相比,各模型组脑缺血后两侧脑组织细胞外液中5种物质水平均升高;与模型组比较,ECH高、低剂量组与CXQ组5种物质的峰值含量均有所降低。结论:大鼠脑缺血后,非缺血区单胺类神经递质及代谢产物升高,ECH对抗脑缺血损伤的作用可能与降低脑内单胺类神经递质的升高有关。     

钩藤碱对脑缺血大鼠纹状体及海马单胺类递质含量的影响(英文)

目的　探索钩藤碱对大鼠脑缺血损伤的机制。方法　采用大鼠大脑中动脉缺血模型 ,利用微透析方法收集正常及脑缺血后不同时间点纹状体和海马细胞外液 (透析液 )。经反相高效液相电化学法检测其单胺类神经递质含量的变化。结果　大鼠脑缺血后纹状体和海马细胞外液中 5 羟吲哚乙酸 (5 HIAA)、3,4 二羟苯酰乙酸 (DOPAC)和高香草酸(HVA)含量下降 ,去甲肾上腺素 (NE)含量上升 ,钩藤碱能升高脑缺血后细胞外液 5 HIAA ,DOPAC和HVA的含量 ,降低NE的含量。结论　钩藤碱能调节脑缺血大鼠纹状体内和海马单胺类神经递质及代谢物的含量     

松果菊苷对6-羟基多巴胺急性损伤大鼠纹状体细胞外液中单胺类递质的影响

目的研究松果菊苷(ECH)对6-羟基多巴胺(6-OH-DA)急性损伤大鼠纹状体细胞外液中单胺类递质的影响,以探讨ECH对脑神经保护作用的可能机制。方法30只大鼠随机分为对照组、模型组、ECH高、低剂量组和美多芭(MD)组。除对照组纹状体内注射等量生理盐水外,其余各组注射6-OHDA4μl(3g·L-1)制作大鼠多巴胺(DA)能神经元损伤的急性模型,术后给予各组动物相应药物或生理盐水腹腔注射,每天1次,于d7进行微透析试验,将透析液注入高效液相—电化学检测器(HPLC-ECD)测定各组纹状体细胞外液中DA、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的含量。结果与对照组相比,模型组动物纹状体细胞外液中DA、DOPAC和HVA含量均明显降低(P<0.01);而ECH高、低剂量组(3.5、7mg.kg-1)和美多芭(MD)组3种物质的含量则高于模型组,两两相比差异具有统计学意义(P<0.05,P<0.01)。结论ECH对6-OHDA急性损伤所致大鼠纹状体细胞外液中的DA及其代谢产物含量减少具有较好的预防作用。     

松果菊苷对帕金森病大鼠纹状体及海马细胞外液中单胺类神经递质的影响

目的研究松果菊苷(echinacoside,ECH)对帕金森病(Parkinson's disease,PD)大鼠纹状体及海马细胞外液中单胺类神经递质的影响,以探讨ECH对脑神经保护作用的可能机制。方法采用双点注射6-羟基多巴胺损毁术制作PD模型,各组大鼠腹腔注射相应的药物或生理盐水连续4周,进行双靶点微透析程序,将透析液注入高效液相-电化学检测器(HPLC-ECD),测定各组大鼠纹状体及海马细胞外液中多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)、去甲肾上腺素(NE)及5-羟色胺(5-HT)的含量。结果与对照组相比,模型组大鼠纹状体及海马细胞外液中NE、DA、DOPAC、HVA、5-HT含量均明显降低(P<0.01);与模型组相比,各给药组大鼠的纹状体及海马细胞外液中5种物质的含量均明显升高(P<0.05,P<0.01);ECH高剂量组与阳性药MD组相差不大。结论 ECH对PD大鼠纹状体及海马细胞外液中的单胺类神经递质的含量减少具有改善作用,对于PD具有一定的治疗作用,这是ECH对PD大鼠脑神经保护作用的可能机制之一。     

L-四氢巴马汀对羟考酮依赖大鼠不同脑区单胺递质水平的影响

目的：观察L-四氢巴马汀（L-THP）对羟考酮依赖大鼠不同脑区单胺递质含量的影响，探讨L—THP对抗羟考酮依赖的机制。方法：以连续递增给药建立羟考酮依赖大鼠模型，L—THP伴随给药，采用HPLC—ECD法测定大鼠前皮层、海马、纹状体和伏隔核内多巴胺（DA）和5-羟色胺（5-HT）含量的变化。结果：与空白对照组相比，羟考酮依赖的大鼠纳络酮催促戒断后前皮层内DA、高香草酸（HVA）和5-HT含量明显降低，伏隔核内DA、3，4-二羟基苯醋酸（DOPAC）、HVA和5-HT含量明显降低，海马内DA、DOPAC、5-HT含量没有明显变化，而5-吲哚乙酸（5-HIAA）明显升高，纹状体内DA及其代谢产物DOPAC、HVA以及5-HT、5-HIAA含量明显降低；L—THP（10，20，30mg&#183;kg^-1，ig）伴随给药，能不同程度抑制上述变化。结论：L—THP可抑制羟考酮依赖引起的不同脑区内单胺类递质含量的变化，提示LTHP对抗羟考酮依赖可能与调节多巴胺和5-HT系统相关。     

用在体脑微透析技术研究大鼠纹状体中单胺递质的释放和代谢

采用脑微透析技术与高效液相色谱-电化学检测器联用测定了清醒自由活动大鼠纹状体细胞外液中多巴胺(DA)及其酸性代谢物3,4-二羟苯乙酸(DOPAC)和高香草酸(HVA)以及5-羟色胺代谢物5-羟吲哚乙酸(5-HIAA)的含量.透析液中DA为0.44 pmol/40μl,DOPAC和HVA含量较DA高约80倍.右旋苯丙胺2 mg/kg,ip使纹状体DA释放显著增加,DOPAC和HVA含量明显下降.     

松果菊苷对脑缺血大鼠纹状体细胞外液中氨基酸水平的影响

目的研究松果菊苷(ECH)对急性脑缺血大鼠纹状体细胞外液中4种氨基酸水平和脑梗死率的影响,以探讨ECH对脑神经保护作用的可能机制。方法 SD大鼠随机分为假手术对照组、模型组、阳性药川芎嗪组(CXQ,40 mg.kg-1)、ECH高剂量(ECH 40 mg.kg-1)组、ECH低剂量(ECH 20mg.kg-1)组和ECH配伍冰片(ECH 40 mg.kg-1,冰片400mg.kg-1)组。各组大鼠给予相应的药物或者生理盐水腹腔注射,每天1次,连续7 d。在给药d 3,脑纹状体埋置探针套管,末次给药1 h后,制作大鼠局灶性脑缺血模型(MCAO),模型成功后立刻进行微透析。将透析液注入高效液相-荧光检测器(HPLC-RF),此方法较氨基酸分析仪相比较,具有最低检测限低等特点,检测各组纹状体细胞外液中天门冬氨酸(Asp)、谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(GABA)的含量。结果与假手术对照组相比,模型组的Asp、Glu、Gly、GABA水平均明显升高;ECH给药组与模型组相比,ECH高剂量组能明显降低Asp、Glu的水平,而ECH低剂量组与ECH配伍冰片组Asp、Glu降低均不明显;ECH高、低组与配伍冰片组对Gly、GABA的影响均不明显;与模型组相比,ECH高、低剂量组能明显地缩小脑梗死面积。结论 ECH对脑神经的保护作用可能与对抗脑缺血后兴奋性氨基酸升高有关。     

白松片对慢性应激大鼠海马单胺类神经递质含量的影响

目的:观察中药白松片对应激大鼠海马单胺类神经递质含量的影响。方法:健康成年雄性SD大鼠42只,随机分为正常对照组、模型对照组、氟西汀对照组(1.8mg·kg-1)及白松片3个剂量(4.32,13.0,21.6g·kg-1,生药量)组。每只大鼠每日灌胃给药1次,连续14d。给药d6始,通过强迫游泳建立应激大鼠模型。用高效液相色谱-电化学法测定大鼠海马单胺类神经递质及其代谢产物的含量。结果:模型对照组大鼠海马去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)含量及多巴胺/3,4-二羟苯乙酸(DA/DOPAC)和5-羟色胺/5-羟吲哚乙酸(5-HT/5-HIAA)的比值分别为(4.7±s1.3)nmol·g-1,(47±12)nmol·g-1,(0.97±0.22)nmol·g-1,19±4,0.23±0.06,低于正常对照组(P<0.05或P<0.01);NE/5-HT比值(4.9±0.9)高于正常对照组(P<0.01);用白松片预防给药可使模型大鼠海马NE,DA和5-HT含量及NE/5HT,DA/DOPAC和5-HT/5-HIAA的比值恢复至正常水平(P<0.05或P<0.01)。结论:白松片可能通过提高NE,DA及5-HT的含量并降低其代谢率来发挥其抗抑郁作用。     

大鼠脑透析液中羟自由基和单胺类递质及其代谢产物同步监测的方法

目的建立同时监测脑透析液中羟自由基和单胺类递质及其代谢产物水平的方法。方法应用脑内微透析技术、水杨酸捕获羟自由基和高效液相-电化学检测器(HPLC-ED)同步监测清醒自由活动大鼠纹状体细胞外液羟自由基和单胺类递质及其代谢产物的水平。结果从NE、EPI、DOPAC、DA、5-H IAA、2,5-DHBA、HVA、2,3-DHBA、3-MT和5-HT的保留时间、最小检测值、标准曲线在20~160μg.L-1浓度范围内与峰高的相关系数、同日4次测定混合标准的变异系数CV等表明本色谱分析的方法是可靠的;R inger液和水杨酸(SASS)-R inger液灌流时纹状体细胞外液单胺类递质及其代谢产物的水平无明显变化(P均>0.05)。SASS-R inger灌流时可测出羟自由基的水平,且不影响单胺类的测定。结论用SASS-R inger灌流收集的透析液可在本实验的条件下,一次进样后同时测定羟自由基和单胺类递质及其代谢产物。     

都可喜对慢性间断性缺氧大鼠学习记忆能力及脑内单胺类神经递质的影响

目的:探讨都可喜(Duxil,阿米三嗪+萝巴新)对慢性间断性缺氧(EHYP)大鼠学习记忆能力和脑内单胺类神经递质水平的影响。方法:建立EHYP大鼠模型,并给予Duxil(0.03片·350g~(-1)体重,bid)干预。用被动避暗回避反射试验评价大鼠学习记忆能力,潜伏期(STL)越长,学习记忆能力越强;用高效液相色谱电化学检测器法测定大鼠皮层、海马和纹状体内去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)等单胺类神经递质的含量。结果:与对照组相比,EHYP组大鼠STL明显缩短(P<0.01),各脑区单胺类神经递质水平显著降低(P<0.05)。与EHYP组相比,Duxil组大鼠STL显著延长(P<0.01),皮层NE和DA含量、海马NE,DA和5-HT含量以及纹状体NE,DA和5-HT含量显著升高(P<0.05)。结论:Duxil可改善EHYP大鼠学习记忆能力并提高脑内单胺类神经递质水平。     

丁基苯酞对大鼠全脑缺血纹状体细胞外液氨基酸和多巴胺含量的影响

用大鼠4动脉阻断全脑缺血模型和大鼠纹状体灌流方法,观察到大鼠急性全脑缺血20min,纹状体细胞外液谷氨酸、牛磺酸、γ-氨基丁酸及多巴胺含量显著升高。丁基苯酞40 mg·kg^-1能使全脑缺血20 min纹状体细胞外液多巴胺及其代谢产物DOPAC含量明显降低,并能降低缺血前后纹状体细胞外液甘氨酸含量,而对谷氨酸等其他氨基酸无显著影响。结果提示丁基苯酞对缺血性脑损伤可能有保护作用。     

The tumour suppressor protein, p53, is involved in the activation of the apoptotic cascade by Delta9-tetrahydrocannabinol in cultured cortical neurons

In gerbils subjected to transient global cerebral ischemia, melanocortin peptides produce long-lasting protection with a broad time window, and through the activation of central nervous system melanocortin MC₄ receptors. Here we aimed to investigate whether melanocortins are neuroprotective also in a rat model of focal cerebral ischemia induced by intrastriatal microinjection of endothelin-1. The vasoconstrictor agent endothelin-1 caused a significant impairment in spatial learning and memory, as well as in sensory-motor orientation and limb use, associated with severe striatal morphological damage including intense neuronal death and an almost complete myelin degradation. Treatment of ischemic rats with a nanomolar dose (340 μg/kg/day i.p. for 11 days, beginning 3 h or 9 h after endothelin-1 microinjection) of the melanocortin analog [Nle⁴, d-Phe⁷]-melanocyte-stimulating hormone (NDP--MSH) significantly reduced striatal damage, and improved subsequent functional recovery, with all scheduled NDP--MSH treatments. Pharmacological blockade of melanocortin MC₄ receptors prevented the protective effect of NDP--MSH. Our findings give evidence that melanocortins are neuroprotective, with a broad time window, also in a severe model of focal cerebral ischemia, and suggest that melanocortin MC₄ receptor agonists could produce neuroprotection in different experimental models of ischemic stroke.     

Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury

This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P < 0.01). Ligustrazine effectively attenuated the detrimental effects of MCAO on the brain. These observations suggest that ligustrazine as a novel cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.     

Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats

We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.     

The effects of systemically administered taurine and N-pivaloyltaurine on striatal extracellular dopamine and taurine in freely moving rats

The second most abundant cerebral amino acid, taurine, is widely consumed in the so-called "energy drinks". Therefore, its possible actions on the brain are of great interest. In the present experiments taurine was given intraperitoneally to rats in order to study if it can be administered systemically in large enough amounts to alter cerebral dopaminergic transmission or to induce hypothermia. In addition, the effects of subcutaneously administered lipophilic taurine analogue, N-pivaloyltaurine, were studied. The extracellular striatal taurine and dopamine concentrations were estimated using in vivo microdialysis in awake and freely moving rats, and the rectal temperatures were measured. Taurine at the total dose of 45 mmol/kg i.p. led to a maximally 8-fold increased striatal extracellular taurine concentration, induced a long-lasting hypothermia, and significantly reduced the striatal extracellular dopamine concentration. The latter effect was strengthened by co-treatment with reuptake inhibitor nomifensine. N-pivaloyltaurine (15 mmol/kg in total, s.c.) only slightly elevated the striatal extracellular taurine concentration, failed to alter the rectal temperature, and in contrast to taurine somewhat elevated the striatal extracellular dopamine concentration suggesting a different mechanism or locus of action from that of taurine. Finally, our experiments using brain microdialysis confirmed the earlier findings that taurine is slowly eliminated from the brain. The results clearly indicate that systemically given taurine enters the brain in concentrations that induce pharmacological effects.     

缺血预适应对沙土鼠脑缺血再灌注后纹状体多巴胺及其代谢产物的影响

目的　研究缺血预适应对沙士鼠脑缺再灌注后纹状体中多巴胺(DA)及其代谢产物的影响,以探讨其神经保护作用的可能机制。方法　应用沙土鼠脑缺血再灌注模型,脑缺血时间为 5min。96只沙土鼠随机分为假手术组 (S)、缺血组(I)、单纯预适应组 (Po)、缺血预适应组 (Ip)。在再灌注 0(即缺血末)、5、30、60min时,断头、分离纹状体,用高效液相-电化学检测器 (HPLC ECD)分别测定各组沙土鼠纹状体DA、3, 4双羟苯乙酸 (DOPAC)和高香草酸 (HVA)的含量。结果　与假手术组相比,短暂缺血组在缺血再灌注期间纹状体中DA、DOPAC和HVA含量均无显著性变化 (P>0 05)。再灌注期间,预适应、缺血再灌注组DA含量均显著低于假手术组,但在再灌注 0min和 30min时,预适应组DA含量及显著高于缺血再灌注组,分别增加了 28% (P<0 01)和 22% (P<0 05)。与假手术组相比,预适应组的DOPAC和HVA含量在再灌注期间均无显著变化 (P>0 05 );缺血再灌注组DOPAC含量在再灌注 5min时有明显增加;HVA含量在再灌注 30min时增加至峰值。结论　缺血预适应能部分抑制沙土鼠脑缺血再灌注期间纹状体DA的降低,显著减少DA氧化代谢产物的产生,从而在脑缺血再灌注损伤中起保护作用。     

褪黑激素降低脑缺血再灌注中羟自由基的生成

目的：研究褪黑激素对大鼠脑缺血再灌注中羟自由基生成的影响。方法：采用栓线法阻塞左侧ＭＣＡ３０ｍｉｎ再灌注模型。通过水杨酸捕获法与微透析技术结合来观察缺血再灌中羟自由基含量的变化。结果：ＤＨＢＡ水平在缺血１５ｍｉｎ后显升高，持续到再灌注后３０ｍｉｎ仍维持较高水平。缺血前３０ｍｉｎ给予ｍｅｌａｔｏｎｉｎ（４ｍｇ·ｋｇ＾－１，ｓｃ）显降低缺血１６￣３０ｍｉｎ及再灌注１－３０ｍｉｎ时ＤＨＢＡ的含量。结     

Enhanced motor activity and brain dopamine turnover in mice during long-term nicotine administration in the drinking water

Nicotine was administered chronically to NMRI mice in their drinking water in gradually increasing concentrations to measure gross motor activity and brain nicotine concentrations over 24 h on the 50th day of nicotine administration. Also, the striatal postmortem tissue concentrations and accumbal extracellular concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured to study the role of dopaminergic systems in nicotine-induced hyperactivity in mice. The cerebral nicotine concentration was at its highest at the end of the dark period. The activity of nicotine-treated mice and their striatal DA metabolism were parallelly increased at 2 to 3 h after midnight and in the forenoon. Microdialysis experiments carried out in the forenoon showed that the extracellular levels of DA and DOPAC were elevated in the nucleus accumbens of these mice. Nicotine did not alter the circadian rhythmicity of activity in the mice. Rather, our findings suggest that the mice consume more nicotine when active and this might lead to enhanced release and metabolism of DA and further, to enhanced motor behavior. These findings support the suggestions that nicotine's effects on limbic and striatal DA are critical for its stimulating effects.