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热刺激前庭在鱼藤酮帕金森病模型中改善运动症状和抑制神经元变性的作用-一项实验研究。

Role of caloric vestibular stimulation in improvement of motor symptoms and inhibition of neuronal degeneration in rotenone model of Parkinson's disease - An experimental study.

机构信息

1Department of Physiology, Saveetha Medical College Hospital, Saveetha Nagar, Thandalam, Chennai 602105, Tamil Nadu, India.

2Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, Tamil Nadu, India.

出版信息

Physiol Int. 2020 Oct 3;107(3):390-405. doi: 10.1556/2060.2020.00036. Print 2020 Oct 17.

Abstract

OBJECTIVE

Parkinson's disease (PD) is a progressive neurodegenerative disorder. In order to explore a noninvasive treatment of PD, in the current study the authors evaluated the neuroprotective efficacy of caloric vestibular stimulation (CVS) using the rotenone-induced rat model of PD. The rotenone models of PD are gaining attention due to high reproducibility. It is also considered to be an improved model to exhibit the pathogenesis of PD and test the neuroprotective effect of various therapeutic interventions.

MATERIALS AND METHODS

Rotenone was i.p. injected (3 mg/kg body weight) to male Wistar albino rats for 21 days to induce PD. As PD is chronic and progressive in nature, the efficacy of chronic CVS intervention was evaluated for 30 days after inducing PD in rats. Motor symptoms were evaluated by assessing locomotor activity in actophotometer, whereas movement analysis was done using Ludolph test and motor coordination was evaluated using rotarod apparatus. The neurochemical and neuropathological changes were also observed in the corpus striatum of rats.

RESULTS

Rotenone administration showed decreased locomotor activity, motor coordination and general movement associated with significant (P < 0.05) reduction in dopamine content in the corpus striatum. The immunohistochemical analysis revealed a marked decrease in tyrosine hydroxylase (TH) immunoreactivity in striatal neurons indicating the significant loss of dopaminergic neurons in substantia nigra (SN) following rotenone injection. However, chronic treatment with CVS restored the nerve terminals in the striatum from rotenone damage. CVS treatment improved the dopaminergic system function by restoring dopamine content in the striatum. CVS also improved the motor deformities clearly suggesting the neuroprotective function.

CONCLUSION

The results of the present study suggested CVS to be a safe and simple neuroprotective measure against neurodegenerative changes in PD and a promising noninvasive technique to overcome the motor symptoms associated with it. The findings could be useful for further investigations and clinical applications of CVS in the treatment of PD.

摘要

目的

帕金森病(PD)是一种进行性神经退行性疾病。为了探索 PD 的非侵入性治疗方法,本研究作者评估了热刺激前庭(CVS)对鱼藤酮诱导的 PD 大鼠模型的神经保护作用。鱼藤酮 PD 模型由于具有较高的重现性而受到关注。它也被认为是一种改进的模型,可以表现出 PD 的发病机制,并测试各种治疗干预措施的神经保护作用。

材料和方法

雄性 Wistar 白化大鼠腹腔内注射鱼藤酮(3mg/kg 体重)21 天诱导 PD。由于 PD 是慢性和进行性的,因此在诱导 PD 后 30 天评估慢性 CVS 干预的疗效。通过评估活动光度计中的运动活动来评估运动症状,使用 Ludolph 测试进行运动分析,使用旋转棒装置评估运动协调。还观察了大鼠纹状体的神经化学和神经病理学变化。

结果

鱼藤酮给药显示运动活动、运动协调和一般运动减少,与纹状体多巴胺含量显著降低(P<0.05)相关。免疫组织化学分析显示纹状体神经元中酪氨酸羟化酶(TH)免疫反应性明显降低,表明鱼藤酮注射后黑质(SN)中多巴胺能神经元大量丢失。然而,CVS 的慢性治疗恢复了纹状体中神经末梢免受鱼藤酮损伤。CVS 通过恢复纹状体中的多巴胺含量来改善多巴胺能系统功能。CVS 还明显改善了运动畸形,明显提示了其神经保护作用。

结论

本研究结果表明 CVS 是一种安全且简单的神经保护措施,可对抗 PD 中的神经退行性变化,并为克服与之相关的运动症状提供了一种有前途的非侵入性技术。这些发现可能对 CVS 在 PD 治疗中的进一步研究和临床应用有用。

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