帕金森病小鼠和大鼠模型黑质纹状体中胆绿素还原酶B的表达

目的探讨胆绿素还原酶B(biliverdin-Ⅸβreductase,BVRB)在1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine,MPTP)帕金森小鼠模型和6-羟基多巴(6-hydroxydopamine,6-OHDA)帕金森大鼠模型黑质-纹状体内的表达。方法通过高效液相色谱的方法检测纹状体内多巴胺及其代谢产物的含量,通过免疫印迹的方法检测黑质纹状体内酪氨酸羟化酶(tyrosine hydroxylase,TH)的表达,以确认模型的成功建立。对黑质纹状体BVRB的表达进行免疫印迹分析。结果与正常对照组相比,MPTP小鼠及6-OHDA大鼠模型纹状体内多巴胺及其代谢产物的含量均明显下降(P<0.01),黑质纹状体内TH表达水平也明显下降(P<0.05),而黑质纹状体BVRB的表达水平在两种模型中均明显增高(P<0.05)。结论黑质纹状体BVRB的高表达可能与帕金森病的氧化应激机制相关。     

黄芩总黄酮对大鼠脑核团单胺类递质的影响

目的研究黄芩总黄酮对大鼠脑内不同神经核团中单胺类神经递质的影响。方法用高效液相色谱-电化学检测法,测定大鼠静脉给予单剂量黄芩总黄酮后单胺类神经递质及代谢产物在脑内不同神经核团的含量变化。结果给予大鼠黄芩总黄酮后,海马和皮层中多巴胺的含量升高,而纹状体内多巴胺的含量降低。结论黄芩总黄酮影响大鼠脑内不同神经核团多巴胺的含量,在海马纹状体影响明显。     

复方海蛇胶囊与多巴丝肼片合用对帕金森病大鼠的作用

目的：研究中药复方海蛇胶囊与多巴丝肼片合用对帕金森病（PD）大鼠的影响,探讨两药合用的增效减毒作用。方法：采用SD大鼠脑右侧黑质致密部注射6-羟基多巴胺造成偏侧PD大鼠模型。给予中药复方海蛇胶囊与多巴丝肼片合用治疗28d后,观察各组PD大鼠行为学改变情况;通过胃肠推进功能实验观察合用药物对PD大鼠胃肠道功能的影响;利用高效液相-电化学检测器检测PD大鼠纹状体内单胺神经递质的含量变化。结果：复方海蛇胶囊与多巴丝肼片两药合用显著减少PD大鼠的旋转圈数,增强PD大鼠的胃肠蠕动能力,明显改善多巴丝肼片对胃肠道的副作用．显著增加PD大鼠纹状体内单胺神经递质的含量。结论：复方海蛇胶囊与多巴丝肼片合用治疗帕金森病．可以起到增强治疗效果、减少多巴丝肼毒性的作用。     

帕金森大鼠模型的MRI、1H-MRS及CT灌注成像的研究

目的 探讨质子磁共振波谱(1H-MRS)及CT灌注(CTP)成像在帕金森病(PD)大鼠模型纹状体内的变化及在PD大鼠模型中的应用.方法 大鼠分为模型组、假手术组及正常组各10只.模型组6-羟基多巴(6-OHDA)于右侧黑质致密部注射成模.三组同期饲养6个月后,以7.0Tesla小动物专用磁共振仪对三组大鼠脑部行MRI平扫、MR血管成像(MRA);双侧纹状体行1H-MRS及CTP灌注检测;检测后处死模型组大鼠,用电镜观察纹状体及黑质超微结构变化.结果 三组大鼠MRI平扫及MRA成像在形态学未见异常.模型组大鼠毁损侧纹状体内N-乙酰门冬氨酸(NAA)/肌酸(Cr)比值明显低于对侧及假手术、正常组的两侧(P<0.01),三组大鼠双侧纹状体内胆碱(Cho)/Cr比值均无显著差异.模型组大鼠毁损侧纹状体部的脑血流量(CBF)、脑血容量(CBV)较对侧及假手术、正常组的两侧减低(P<0.05).电镜观察模型组大鼠病侧纹状体及黑质部存在超微结构改变.结论 1H-MRS和CTP检测可以为PD大鼠模型纹状体部位的代谢及病理学改变提供有价值的信息.     

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。     

柔性纳米脂质体介导脑源性神经营养因子经鼻给药治疗帕金森病的研究

目的 研究柔性纳米脂质体介导脑源性神经营养因子(brain derived neurotrophic factor,BDNF)经鼻给药治疗帕金森病的有效性及安全性。方法 采用注入法制备BDNF柔性纳米脂质体(BDNF-FNL),建立大鼠帕金森模型,将建模成功的大鼠随机分为模型组、BDNF溶液组及BDNF-FNL组,并以正常大鼠作空白对照,分别经鼻给药后于0.5,1,1.5,2 h测定BDNF在脑组织中的含量变化,以鼻黏膜组织病理改变初步判断该途径给药的鼻腔安全性,通过实验组大鼠的行为学变化、黑质酪氨酸羟化酶免疫阳性神经元的变化以及脑内纹状体3种单胺类神经递质(多巴胺、多巴柯和高香草酸)的含量变化评价其对帕金森病模型大鼠多巴胺神经元的修复作用。结果 BDNF-FNL组BDNF的脑组织浓度约是BDNF溶液组的3倍;柔性脂质体经鼻给药后安全性较高,对鼻黏膜无明显损伤;BDNF-FNL组的大鼠行为学改善效果优于BDNF溶液组;TH免疫组化结果表明,柔性纳米脂质体能更好的介导BDNF进入脑部发挥对多巴胺神经元保护作用;且BDNF-FNL组大鼠纹状体中3种单胺类神经递质的含量明显地高于BDNF溶液组及模型组。结论 柔性纳米脂质体能更好地介导BDNF经鼻入脑发挥对帕金森病模型大鼠多巴胺神经元的修复作用,且对鼻黏膜的安全性较好。     

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     

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。     

复方海蛇胶囊对帕金森病小鼠的作用

目的：研究复方海蛇胶囊对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病小鼠的作用。方法：采用C57BL/6J小鼠腹腔注射MPTP制备帕金森病动物模型,给药14 d后观察各组小鼠行为活动变化,利用高效液相-电化学检测器检测纹状体内多巴胺（DA）及其代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）等的含量变化。结果：复方海蛇胶囊可以显著对抗MPTP对黑质及纹状体的损伤作用,明显改善帕金森病的症状;与模型组相比,复方海蛇胶囊治疗后可以显著提高小鼠纹状体内DA、DOPAC和HVA的含量（P〈0.01）。结论：复方海蛇胶囊通过保护多巴胺能神经元,提高纹状体内DA的含量,改善帕金森病的症状。     

无铅汽油染毒对小鼠神经行为和神经递质的影响

目的 研究汽油染毒对小鼠神经行为和单胺类神经递质及其代谢产物的影响。方法 选用80只昆明小鼠，随机分成4组，用无铅汽油静式染毒90d，分别于染毒前和染毒第30、60、90天时测定其自由活动情况及学习和记忆能力，并于染毒第90天时测定其纹状体中儿茶酚胺类神经递质及尿中其代谢产物含量。结果 染毒60d后小鼠自由活动计数增加；染毒30d后水迷宫和跳台法学习能力均下降，且都存在剂量一效应关系；染毒90d后中、高剂量组纹状体单胺类神经递质及尿中单胺类神经递质代谢产物含量均下降。结论 长期无铅汽油接触可以引起小鼠神经行为的改变，其机制可能与单胺类神经递质及其代谢产物的含量减少有关。     

Effects of tetrahydroxystilbene glucoside in Parkinson′s disease mice model induced by MPTP

OBJECTIVE To observe effects of tetrahydroxystilbene glucoside(TSG)on behavior,content of dopamine and its metabolites in striatum of Parkinson′s disease(PD)model mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)injection.METHODS Mice were randomly divided into control group,model group,TSG low dose(60mg·kg-1)and high dose(120mg·kg-1)groups.The behavior changes of mice were observed by pole test,rotarod test and spontaneous movement test.The tyrosine hydroxylase(TH)positive cells were detected by immunohistochemical method.The content of dopamine(DA)and its metabolites in striatum were determined by HPLC-ECD.RESULTS MPTP model mice showed behavior deficit.The number of TH positive neurons in substantia nigra,the content of dopamine and its metabolites in striatum in model mice decreased significantly compared with control group.TSG ameliorated mice behavior,increased the number of TH positive neurons in the substantia nigra about 18.8%,and elevated the content of dopamine in striatum about 34.5% compared with model mice.CONCLUSION TSG protected dopaminergic neurons against MPTP-induced damage,and may become a candidate drug for prevention and treatment of Parkinson′s disease.     

Neuroprotection by crocetin in a hemi-parkinsonian rat model

Reactive oxygen species (ROS) are implicated as the leading biochemical cause of neuronal death in various neurologic disorders, including Parkinson's disease. In the present study, neuromodulatory effects of crocetin (active constituent of Crocus sativus) in a 6-hydroxydopamine (6-OHDA) model of rat Parkinsonism were investigated. Male Wistar rats were pre-treated with crocetin (25, 50 and 75 microg/kg body weight) for 7 days and subjected to unilateral intrastriatal injection of 10 microg 6-OHDA on day 8. Locomotion and rotation were observed on day 23 post-injection, and after 4 weeks, striatum and substantia nigra were dissected out by decapitation. Activity of antioxidant enzymes and content of dopamine (DA) and its metabolites were estimated in striatum, whereas glutathione (GSH) content and thiobarbituric acid reactive substance (TBARS) were evaluated in substantia nigra. Levels of GSH and dopamine were protected, while TBARS content was attenuated in crocetin-treated groups. The activity of antioxidant enzymes was decreased in the lesion group, but protected in the crocetin-treated groups. These findings were supported by the histopathologic findings in the substantia nigra that showed that crocetin protects neurons from deleterious effects of 6-OHDA. This study revealed that crocetin, which is an important ingredient of diet in India and also used in various systems of indigenous medicine, is helpful in preventing Parkinsonism and has therapeutic potential in combating this devastating neurologic disorder.     

Toxicity of p-methoxyphenol to dopamine neurons in the rat substantia nigra

Local injections of p-methoxyphenol into the substantia nigra of rats led to a mildly dose-related destruction of dopamine neurons as indicated by reductions of dopamine and its metabolites in the ipsilatera1 striatum and by loss of tyrosine hydroxylase immunoreactivity in the injected substantia nigra. Both Nissl staining of the injected nucleus and measurement of noradrenaline and serotonin in the ipsilatera1 striatum indicated some selectivity of the toxic action.     

Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway

Background and purpose:

We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin-like growth factor-I receptor (IGF-IR) signalling pathway in human breast cancer MCF-7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF-IR signalling pathway in a rat model of Parkinson''s disease, induced by 6-hydroxydopamine (6-OHDA).

Experimental approach:

Ovariectomized rats were infused unilaterally with 6-OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6-OHDA injections) in the absence or presence of the IGF-IR antagonist JB-1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl-2 in the substantia nigra were also determined.

Key results:

Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB-1. 6-OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6-OHDA-lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl-2 protein and gene level in the substantia nigra. These effects were abolished by JB-1.

Conclusions and implications:

These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6-OHDA model of nigrostriatal injury and its actions might involve activation of the IGF-IR signalling pathway.     

Assessing an eating disorder induced by 6-OHDA and the possibility of nerve regeneration therapy by transplantation of neural progenitor cells in rats.

Parkinson's disease is a neurodegenerative disorder of the substantia nigra accompanied by the depletion of dopamine levels. Symptoms of Parkinson's disease involve motor disorders, including dysphagia and aspiration. In this study, rats were injected with 6-hydroxydopamine (6-OHDA) in order to assess the eating disorder and evaluate the effect of transplantation of neural progenitor cells (NPCs). The administration of 6-OHDA resulted in an extension of feeding time and a marked increase in the amount of feed powder on the cage floor after feeding at 2 and 4 weeks after 6-OHDA. These rats had NPCs obtained from the brains of newborn rats transplanted into their striata 2 weeks after 6-OHDA injection. The treatment shortened the feeding time and decreased the amount of feed powder on the cage floor after feeding. The 6-OHDA injection decreased the number of tyrosine hydroxylase-positive cells in the striatum and substantia nigra, and NeuN in the solitary tract. A greater number of tyrosine hydroxylase-positive cells in the substantia nigra and NeuN-positive cells in the solitary tract were detected in the animals transplanted with NPCs than the 6-OHDA injected control. The NPCs labeled with 5-bromo-2'-deoxyuridine were detected in the striatum, but not in the substantia nigra and solitary tract. These results may suggest that the eating disorder induced by 6-OHDA may be related to neural damage to the substantia nigra and/or solitary tract. Transplantation of NPCs may cure 6-OHDA-induced eating disorders accompanied by the protection of neurons from the toxin.     

The antioxidant drink effective microorganism-X (EM-X) pre-treatment attenuates the loss of nigrostriatal dopaminergic neurons in 6-hydroxydopamine-lesion rat model of Parkinson's disease

There is continued interest in the assessment and potential use of antioxidants as neuroprotective agents in diseases associated with increased oxidative stress, such as Parkinson's disease. The neuroprotective effect of a natural antioxidant drink, EM-X (a ferment derivative of unpolished rice, papaya and seaweeds with effective microorganisms), was investigated using the 6-hydroxydopamine (6-OHDA)-lesion rat model of Parkinson's disease. The nigrostriatal dopaminergic neurons were unilaterally lesioned with 6-OHDA (8 microg) in rats that were treated with a 10-times diluted EM-X drink (dilEM-X), standard EM-X drink (stdEM-X) or tap water for 4 days. Seven days post lesion, the integrity (no. of tyrosine hydroxylase positive cells (TH+ cells) in the substantia nigra pars compacta (SNpc)) and functionality (dopamine and its metabolites DOPAC and HVA content in the striata) of nigrostriatal dopaminergic neurons were assessed. In the vehicle-treated rats, infusion of 8 microg of 6-OHDA significantly reduced the number of TH+ cells in the SNpc as well as the levels of dopamine, DOPAC and HVA in the striata on the lesion side. The loss of TH+ cells, dopamine and HVA, but not the DOPAC levels, was significantly attenuated by stdEM-X pretreatment, but not by the dilEM-X pretreatment. There were no significant changes in the TH+ cells, or in the monoamine levels with the EM-X pretreatment per se, except for a small but significant fall in the levels of dopamine with the stdEM-X. The evidence presented supports the potential neuroprotective effects of stdEM-X drink, although its effect on dopamine levels needs further investigation.     

慢病毒介导的新型Tet-On系统大鼠GDNF和TH双基因脑内转移对帕金森病大鼠模型的保护作用

目的探讨慢病毒介导的新型Tet-On系统大鼠胶质细胞源性神经营养因子(GDNF)基因和酪氨酸羟化酶(TH)双基因直接转移对帕金森病(PD)大鼠的保护作用。方法将携带TH、GDNF基因并含启动子为Palb的四环素应答元件的慢病毒(Lv-TH-GDNF)和四环素反式作用子rtTA2s-M2病毒共同注射到SD大鼠左侧纹状体,用强力霉素(DOX)诱导大鼠目的基因GDNF和TH的表达。1周后在大鼠的同侧纹状体注射6-羟基多巴胺(6-OHDA)损毁纹状体的DA能神经元。通过旋转行为、黑质TH免疫组化染色以及高效液相色谱-电化学方法(HPLC-ECD)检测纹状体DA含量评估其保护效应;通过RT-PCR、免疫印迹观察Lv-TH-GDNF在脑内的表达。实验与健康对照组、磷酸缓冲液(PBS)对照组进行比较。结果在6-OHDA损伤后4周,Lv-TH-GDNF+rt-TA2s-M2+DOX组大鼠阿扑吗啡诱发的旋转效应均明显低于PBS对照组(P<0.01),损毁侧的的黑质区TH阳性细胞表达强度、纹状体DA含量均明显高于PBS对照组(P<0.01),但二者均低于健康对照组(P<0.01)。RT-PCR、免疫印迹结果显示,与PBS对照组比较,Lv-TH-GDNF+rtTA2s-M2+DOX组大鼠纹状体TH、GDNF基因的表达明显增高(P<0.01)。结论慢病毒介导的新型Tet-On系统大鼠GDNF和TH双基因脑内直接转移,在强力霉素诱导下可减缓6-OHDA诱发的大鼠DA能神经元进行性变性,具有保护作用。     

Attenuation by Nardostachys jatamansi of 6-hydroxydopamine-induced parkinsonism in rats: behavioral, neurochemical, and immunohistochemical studies

Parkinson's disease (PD) is one of the commonest neurodegenerative diseases, and oxidative stress has been evidenced to play a vital role in its causation. In the present study, we evaluated whether ethanolic extract of Nardostachys jatamansi roots (ENj), an antioxidant and enhancer of biogenic amines, can slow the neuronal injury in a 6-OHDA-rat model of Parkinson's. Rats were treated with 200, 400, and 600 mg/kg body weight of ENj for 3 weeks. On day 21, 2 microl of 6-OHDA (12 microg in 0.01% in ascorbic acid-saline) was infused into the right striatum, while the sham-operated group received 2 microl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioural activity and were sacrificed after 6 weeks for the estimation of lipid peroxidation, reduced glutathione content, the activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase, quantification of catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by ENj. Lesioning was followed by an increased lipid peroxidation and significant depletion of reduced glutathione content in the substantia nigra, which was prevented with ENj pretreatment. The activities of glutathione-dependent enzymes, catalase and superoxide dismutase in striatum, which were reduced significantly by lesioning, were dose-dependently restored by ENj. A significant decrease in the level of dopamine and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, and both were significantly recovered following ENj treatment. All of these results were exhibited by an increased density of tyrosine hydroxylase immunoreactive (TH-IR) fibers in the ipsilateral striatum of the lesioned rats following treatment with ENj; 6-OHDA injection had induced almost a complete loss of TH-IR fibers. This study indicates that the extract of Jatamansi might be helpful in attenuating Parkinsonism.     

Protective effects of ethanolic extract of Delphinium denudatum in a rat model of Parkinson's disease

Parkinson's disease (PD) is one of the major neurodegenerative disorders, and oxidative stress has been implicated in playing an important role in the pathogenesis of the disease. In the present study, we investigated if Delphinium denudatum extract can slow down the neuronal injury in 6-hydroxydopamine (6-OHDA) rat model of Parkinsonism. Rats were treated with 200, 400 and 600 mg/kg body weight (b.w.) of D. denudatum extract for 3 weeks. On day 22, 2 microL of 6-OHDA (10 microg in 0.1% ascorbic acid-saline) or vehicle was infused into the right striatum of the animals. Three weeks after the 6-OHDA injections, the rats were killed for estimation of lipid peroxidation (LPO), reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities, catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase (TH) expression. Increased LPO and significant depletion of reduced GSH content in the substantia nigra resulting from the lesion were appreciably prevented with Delphinium treatment. Delphinium extract also dose-dependently attenuated the activities of SOD and CAT in striatum, which had been reduced significantly by lesioning. A significant decrease in the level of dopamine (DA) and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both parameters were significantly recovered with treatment of the extract. Finally, all these results were confirmed by an increase in expression of TH in the ipsilateral striatum of the lesioned groups following treatment with Delphinium extract. Thus, the study indicates that D. denudatum extract may be helpful in checking neuronal injury in Parkinsonism.     

Neurotoxic effects of berberine on long-term l-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease

The effects of berberine on long-term administration of l-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease (PD) were investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral sides, and then were treated with berberine (5 and 15 mg/kg) and/or l-DOPA (10 mg/kg) once daily for 21 days. Treatments with either concentration of berberine (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition, dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned groups was attenuated by l-DOPA administration. However, both concentrations of berberine in 6-OHDA-lesioned groups treated with l-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic l-DOPA administration. Long-term l-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms.