Gilmour Gary, Iversen Susan D, O'Neill Michael F, Bannerman David M
Eli Lilly and Co. Ltd., Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK.
Behav Brain Res. 2004 Apr 2;150(1-2):171-83. doi: 10.1016/j.bbr.2003.07.006.
Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.
诱导实验性脑损伤的不同方法可导致不同的神经病理学后遗症。这对于建立中风后功能恢复的动物模型可能具有重要意义，因为实验性损伤病理学进展的差异可能会影响使用任何特定损伤方法观察到的功能恢复程度和速度。在本研究中，将通过皮质内微注射内皮素-1（ET-1）产生局灶性缺血性损伤的新方法与兴奋性毒性（微注射喹啉酸）和机械性（抽吸）损伤程序进行了比较。损伤为单侧，靶点是感觉运动皮层的前肢代表区。研究发现，在抓 paw 任务的到达准确性方面，所有三种类型的损伤具有基本相同的效果。与假手术动物相比，所有损伤动物在到达准确性方面均表现出相似的、显著的长期缺陷以及有限的恢复程度。对损伤后第9周动物行为表现的离线分析表明，每个损伤组的动物也表现出相似的缺陷。目前的结果表明，大鼠单侧FL损伤的自发行为后果似乎与损伤产生的性质无关。然而，ET-1诱导损伤的表面效度增加，再加上该技术在损伤位置和范围控制上的便利性，使其成为研究药物对中风后功能恢复影响的潜在重要动物模型。
