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用于将药物长期递送至腰蛛网膜下腔的年轻大鼠寰枕部导管置管术,结合体内检测和原位电生理学。

Atlanto-occipital catheterization of young rats for long-term drug delivery into the lumbar subarachnoid space combined with in vivo testing and electrophysiology in situ.

机构信息

Bogomoletz Institute of Physiology, Bogomoletz str. 4, Kyiv 01024, Ukraine; Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.

Bogomoletz Institute of Physiology, Bogomoletz str. 4, Kyiv 01024, Ukraine.

出版信息

J Neurosci Methods. 2017 Oct 1;290:125-132. doi: 10.1016/j.jneumeth.2017.08.001. Epub 2017 Aug 2.

Abstract

BACKGROUND

Catheterization has been widely used in neuroscience and pain research for local drug delivery. Though different modifications were developed, the use of young animals for spinal catheterization remains limited because of a little success rate. A reliable technique is needed to catheterize young animals aimed for in vivo testing combined with spinal cord electrophysiology, often limited by animal age, to facilitate pain research.

NEW METHODS

We describe intrathecal catheterization of young rats (3-week-old) through atlanto-occipical approach for long-lasting drug delivery into the lumbar subarachnoid space. The technique represents a surgical approach of minimized invasiveness that requires PE-10 catheter and few equipment of standard laboratory use.

RESULTS

Behavioral assessments revealed that spinal catheterization does not change peripheral sensitivity of different modalities (thermal and mechanical) and gives no rise to locomotive deficit or anxiety-like behavior in young rats. The long-term administration of genetic material (oligodeoxynucleotides given up to 4days), examined both in vivo and in situ, produced no adverse effects on basal peripheral sensitivity, but changed the AMPA receptor-mediated currents in sensory interneurons of the spinal cord.

COMPARISON WITH EXISTING METHODS

Dissimilar to already described methods, the method is designed for the use of young rats for behavioral testing in vivo and/or spinal cord electrophysiology in situ.

CONCLUSIONS

A practical method for spinal catheterization of young animals designed for studies in vivo and in situ is proposed. The method is rapid and effective and should facilitate investigation of therapeutic effects on both systemic and subcellular levels, as an advantage over the existing methods.

摘要

背景

在神经科学和疼痛研究中,导管插入术已被广泛用于局部药物输送。尽管已经开发出了不同的改良方法,但由于成功率较低,年轻动物的脊髓导管插入术的应用仍然受到限制。需要一种可靠的技术,以便对年轻动物进行导管插入术,以进行体内测试,并结合脊髓电生理学,通常受动物年龄限制,以促进疼痛研究。

新方法

我们描述了通过寰枕入路对 3 周龄的幼鼠进行鞘内导管插入术,以将药物长期输送到腰蛛网膜下腔。该技术代表了一种微创性的手术方法,需要使用 PE-10 导管和一些标准实验室设备。

结果

行为评估表明,脊髓导管插入术不会改变不同模式(热和机械)的外周敏感性,并且不会导致幼鼠出现运动功能障碍或焦虑样行为。长达 4 天的遗传物质(寡核苷酸)的长期给药,无论是在体内还是在原位进行检查,都不会对基础外周敏感性产生不利影响,但会改变脊髓感觉中间神经元中 AMPA 受体介导的电流。

与现有方法的比较

与已经描述的方法不同,该方法专为年轻动物的体内行为测试和/或原位脊髓电生理学设计。

结论

提出了一种用于年轻动物脊髓导管插入术的实用方法,可用于体内和原位研究。该方法快速有效,应该优于现有方法,有利于在系统和亚细胞水平上研究治疗效果。

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