PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is one of the most common neurodegenerative diseases worldwide. Currently applied therapeutic protocols are limited to improve the motor functions of patients. Therefore, seeking alternative regimes with better therapeutic impact is crucial. This study aims to validate the therapeutic impact of mesenchymal stem cell injection using two delivery methods, intracranial administration and intravenous administration, on rotenone (ROT)-induced PD model in rats. Our work included behavioral, biochemical, histological, and molecular investigations. Open field test (OFT) and rotarod tests were applied. Important oxidative stress, antioxidant and proinflammatory markers were monitored. Substantia Nigra and Striatum tissues were examined histologically and the molecular expression of DOPA decarboxylase, Tyrosine hydroxylase, and α-synuclein in neurons in these tissues were investigated. Our results showed that MSC grafting improved motor and memory impairments and oxidative stress status that were observed after ROT administration. Additionally, BM-MSCs application restored SOD and CAT activities and the levels of DA, L-Dopa, IL6, IL1β, and TNFα. Moreover, MSC grafting overwhelmed the pathological changes induced by ROT and normalized the expression of Tyrosine hydroxylase, DOPA decarboxylase, and α-synuclein towards the control values in the Nigral and Striatal tissues of male rats. Conclusively, both administration routes improved motor function, protection of the nigrostriatal system, and improved striatal dopamine release. The observed beneficial effect of applying MSCs suggests potential benefits in clinical applications. No significant differences in the outcomes of the treatment would favor a certain way of MSC application over the other. However, the intravenous delivery method seems to be safer and more feasible compared to the intrastriatal method.
摘要：
帕金森病(PD)是世界范围内最常见的神经退行性疾病之一。目前应用的治疗方案仅限于改善患者的运动功能。因此,寻求具有更好治疗效果的替代方案至关重要。本研究旨在验证使用两种递送方法注射间充质干细胞的治疗效果，颅内给药和静脉给药，鱼藤酮（ROT）诱导的大鼠PD模型。我们的工作包括行为，生物化学，组织学,和分子研究。采用开放式现场试验(OFT)和旋转杆试验。重要的氧化应激，监测抗氧化剂和促炎标志物。对黑质和纹状体组织进行组织学检查，并观察DOPA脱羧酶的分子表达，酪氨酸羟化酶,研究了这些组织中神经元中的α-突触核蛋白。我们的结果表明，MSC移植改善了ROT给药后观察到的运动和记忆障碍以及氧化应激状态。此外,BM-MSCs的施用恢复了SOD和CAT的活性和DA的水平,左旋多巴,IL6,IL1β,和TNFα。此外，MSC移植克服了ROT诱导的病理变化，并使酪氨酸羟化酶的表达正常化，多巴脱羧酶,和α-突触核蛋白朝向雄性大鼠黑体和纹状体组织中的对照值。最后，两种给药途径都改善了运动功能，黑质纹状体系统的保护，并改善纹状体多巴胺的释放。观察到的应用MSC的有益效果表明在临床应用中的潜在益处。治疗结果没有显着差异，这将有利于MSC的某种应用方式。然而,与纹状体内给药方法相比，静脉给药方法似乎更安全，更可行。
