Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be ...Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites 展开更多
帕金森病(Parkinson’s disease,PD)主要症状是由中脑黑质致密部(substantia nigra compact,SNc)的多巴胺(dopamine,DA)神经元死亡引起。帕金森病发病过程中,路易小体病理(Lewy pathology,LP)和线粒体功能障碍最为突出,但SNc多巴胺神经...帕金森病(Parkinson’s disease,PD)主要症状是由中脑黑质致密部(substantia nigra compact,SNc)的多巴胺(dopamine,DA)神经元死亡引起。帕金森病发病过程中,路易小体病理(Lewy pathology,LP)和线粒体功能障碍最为突出,但SNc多巴胺神经元为什么特别易遭受这两种病理损害尚不清楚。研究表明,与脑内其他神经元相比,SNc多巴胺神经元具有特殊的解剖形态、生理和生化表型。SNc多巴胺神经元具有高分支无髓鞘轴突和众多的突触终端,突触末梢物质和能量代谢的高要求需要大量的线粒体,巨大突触终端增加了突触蛋白质的表达、转运和降解的负担。SNc多巴胺神经元具有独特的自主起搏电活动和缓慢钙振荡特性,Cav1. 3钙通道活动及后续的级联反应增加了SNc多巴胺神经元线粒体负担,增加了基础氧化应激、线粒体损伤和自噬,降低了处理错误折叠蛋白质的能力。SNc多巴胺神经元特有的神经递质--多巴胺易被氧化成为反应性醌,具有潜在毒性,可破坏葡糖脑苷脂酶导致其活性降低,引起线粒体氧化应激和溶酶体功能障碍。总之,SNc多巴胺神经元具有的这些内在因素综合起来,可能导致了其对线粒体功能障碍和路易小体病理损伤的易感性,并且SNc多巴胺神经元所处的神经网络障碍也促使了帕金森病的进展。认识到这些特征会对研究帕金森病相关病理学机制和阻止疾病进展创造新的机会。展开更多
Background： Numerous studies have demonstrated that patients with Parkinson＆#39;s disease （PD） have a higher prevalence of substantia nigra （SN） hyperechogenicity compared with controls. Our aim was to explore t...Background： Numerous studies have demonstrated that patients with Parkinson＆#39;s disease （PD） have a higher prevalence of substantia nigra （SN） hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography （TCS） of patients with PD and those with PD with dementia （PDD）. The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. Methods： The ratios of SN hyperechogenicity （SN＋）, maximum sizes of SN＋, and widths of third ventricle （TV） were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic （ROC） curve analysis. Results： The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN＋ and maximum sizes of SN＋ between PDD and PD groups （P 〉 0.05）. TV widths were significantly larger in PDD group （7.1± 1.9 mm） than in PD group （6.0± 2.0 mm） and controls （5.9 ± 1.5 mm, P 〈 0.05）; however, the ratios of enlarged TV did not differ among the three groups （P = 0.059）. When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups （P = 0.030） and between PDD group and controls （P = 0.003）, based on ROC curve analysis. In PDD patients, SN＋ was more frequently detected in akinetic-rigid subgroup, and patients with SN＋ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores （P 〈 0.05）. Conclusions： Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 30271441) Key Project of Shandong Educational Committee (J01 K03) and Qingdao Municipal Science & Technology Commission (02-1-KJ-YJ-49).
基金supported by the Medical and Health Technology Development Plan of Shandong Province of China,No.2011HD009(to AHW)the Chinese Medicine Science and Technology Development Plan Project of Shandong Province of China,No.2017-163(to AHW)+1 种基金the Natural Science Foundation of Shandong Province of China,No.ZR2016HP23(to AHW)the Science and Technology Development Plan Project of Taian City of China,No.2017NS0151(to XCS)
文摘Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease.As such,inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease.Ginsenoside Rbl,the most active ingredient of ginseng,reportedly exerts neuroprotective effects by suppressing inflammation in vitro.The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rbl in a lipopolysaccharide-induced rat Parkinson’s disease model.Rats were divided into four groups.In the control group,sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days.In the ginsenoside Rbl group,ginsenoside Rb1(20 mg/kg)was intraperitoneally injected for 14 consecutive days after sham surgery.In the lipopolysaccharide group,a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model.Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days.In the ginsenoside Rbl +lipopolysaccharide group,lipopolysaccharide was unilaterally microinjected into the rat substantial nigra.Subsequently,ginsenoside Rbl was intraperitoneally injected for 14 consecutive days.To investigate the therapeutic effects of ginsenoside Rbl,behavioral tests were performed on day 15 after lipopolysaccharide injection.We found that ginsenoside Rbl treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group.To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rbl,contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography.Compared with the lipopolysaccharide group,ginsenoside Rbl obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites
文摘Background： Numerous studies have demonstrated that patients with Parkinson＆#39;s disease （PD） have a higher prevalence of substantia nigra （SN） hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography （TCS） of patients with PD and those with PD with dementia （PDD）. The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. Methods： The ratios of SN hyperechogenicity （SN＋）, maximum sizes of SN＋, and widths of third ventricle （TV） were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic （ROC） curve analysis. Results： The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN＋ and maximum sizes of SN＋ between PDD and PD groups （P 〉 0.05）. TV widths were significantly larger in PDD group （7.1± 1.9 mm） than in PD group （6.0± 2.0 mm） and controls （5.9 ± 1.5 mm, P 〈 0.05）; however, the ratios of enlarged TV did not differ among the three groups （P = 0.059）. When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups （P = 0.030） and between PDD group and controls （P = 0.003）, based on ROC curve analysis. In PDD patients, SN＋ was more frequently detected in akinetic-rigid subgroup, and patients with SN＋ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores （P 〈 0.05）. Conclusions： Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.
