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在给予内皮素-1诱导的轻度局灶性缺血大鼠的阶梯行走任务中检测慢性感觉运动障碍

Detection of chronic sensorimotor impairments in the ladder rung walking task in rats with endothelin-1-induced mild focal ischemia.

作者信息

Riek-Burchardt Monika, Henrich-Noack Petra, Metz Gerlinde A, Reymann Klaus G

机构信息

Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany.

出版信息

J Neurosci Methods. 2004 Aug 30;137(2):227-33. doi: 10.1016/j.jneumeth.2004.02.012.

Abstract

A comprehensive evaluation of the effects of neuroprotection, neurogenesis, and compensatory mechanisms on the outcome of ischemic insults requires assessment of morphological and functional parameters. Behavioural tests are essential when recording performance throughout the time course of an experiment and the results bear predictive value in preclinical animal models. The goal of this study was to establish a behavioural test procedure for a model of transient focal ischemia induced by injection of endothelin-1 (eMCAO) that results in relatively mild behavioural deficits. The test protocol used in the present study allows evaluation of quantitative and qualitative impairments in skilled motor performance and is sensitive to detect chronic deficits at chronic post-ischemic time intervals. The ladder rung walking task [J. Neurosci. Methods 115 (2002) 169] is a motor test that assesses skilled walking and measures both forelimb and hindlimb placing, stepping and inter-limb co-ordination. In this study we tested the effect of two different technical variants of endothelin-1 application on infarct volume and motor skills (1) application via pre-implanted guiding cannula in awake animals and (2) via direct injection under halothane anaesthesia. We showed that the ladder rung walking task is sensitive in the assessment of loss of fine motor function after induction of relatively small lesions. In animals with implanted cannulas we found a smaller infarct area and an increase in placement errors prior to ischemia animals with eMCAO under anaesthesia showed a long lasting impairment of the contralateral forelimb up to 4 weeks post-eMCAO.

摘要

对神经保护、神经发生和代偿机制对缺血性损伤结果的影响进行全面评估,需要对形态学和功能参数进行评估。在整个实验过程中记录行为表现时,行为测试至关重要,并且这些结果在临床前动物模型中具有预测价值。本研究的目的是为通过注射内皮素-1诱导的短暂性局灶性缺血模型(eMCAO)建立一种行为测试程序,该模型会导致相对较轻的行为缺陷。本研究中使用的测试方案允许评估熟练运动表现中的定量和定性损伤,并且在缺血后慢性时间间隔内对检测慢性缺陷很敏感。阶梯行走任务[《神经科学方法杂志》115(2002)169]是一种运动测试,用于评估熟练行走,并测量前肢和后肢的放置、迈步以及肢体间的协调性。在本研究中,我们测试了两种不同技术变体的内皮素-1应用对梗死体积和运动技能的影响:(1)在清醒动物中通过预先植入的引导套管应用,以及(2)在氟烷麻醉下直接注射。我们表明,阶梯行走任务在评估相对较小损伤诱导后精细运动功能丧失方面很敏感。在植入套管的动物中,我们发现梗死面积较小,并且在缺血前放置错误增加;在麻醉下进行eMCAO的动物中,对侧前肢在eMCAO后长达4周都存在长期损伤。

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