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在半帕金森病的6-羟基多巴胺模型中,将负载多巴胺的可生物降解水凝胶单侧植入纹状体可减轻运动异常。

Unilateral implantation of dopamine-loaded biodegradable hydrogel in the striatum attenuates motor abnormalities in the 6-hydroxydopamine model of hemi-parkinsonism.

作者信息

Senthilkumar Karuppagounder S, Saravanan Karuppagounder S, Chandra Goutam, Sindhu Kizhakke M, Jayakrishnan A, Mohanakumar Kochupurackal P

机构信息

Division of Cell Biology & Physiology, Laboratory of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.

出版信息

Behav Brain Res. 2007 Nov 22;184(1):11-8. doi: 10.1016/j.bbr.2007.06.025. Epub 2007 Jul 5.

Abstract

Dopaminergic functional recovery following controlled release of dopamine from biodegradable polymer matrices implanted in the lesioned striatum was investigated in a hemiparkinsonian animal model. Significant dopamine depletion in the striatum ipsilateral to the side of infusion was observed in animals unilaterally infused with 6-hydroxydopamine (6-OHDA) in the substatia nigra. These animals displayed apomorphine-induced contralateral rotational behavior, when examined on the 16th day. Implantation of a controlled release delivery system (hydrogel obtained by mixing dextran dialdehyde cross-linked with gelatin) containing dopamine in the denervated striatum on the 1st day or the 18th day significantly abolished the apomorphine-induced contralateral rotational behavior in these animals. The recovery was visible for about 17 days, thereafter the behavioral bias reappeared. The present results indicate that dopamine released from the polymer matrices alleviates behavioral bias in experimental parkinsonism, implying use of such technologies as an alternative method for the treatment of Parkinson's disease. This approach is useful in reducing the oral dose of drugs that are with severe systemic effects, and that develop tolerance.

摘要

在半帕金森病动物模型中,研究了将多巴胺从植入受损纹状体的可生物降解聚合物基质中控制释放后多巴胺能功能的恢复情况。在单侧黑质注射6-羟基多巴胺(6-OHDA)的动物中,观察到注射侧同侧纹状体中多巴胺显著耗竭。在第16天检查时,这些动物表现出阿扑吗啡诱导的对侧旋转行为。在第1天或第18天,将含有多巴胺的控释给药系统(通过将葡聚糖二醛与明胶交联得到的水凝胶)植入去神经支配的纹状体中,可显著消除这些动物中阿扑吗啡诱导的对侧旋转行为。恢复情况持续约17天,此后行为偏差再次出现。目前的结果表明,从聚合物基质中释放的多巴胺可减轻实验性帕金森病中的行为偏差,这意味着可将此类技术用作治疗帕金森病的替代方法。这种方法有助于减少具有严重全身效应且会产生耐受性的药物的口服剂量。

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