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评估表皮生长因子受体(EGFR)抑制剂治疗对大鼠胸段脊髓损伤后膀胱和运动功能恢复的影响。

A re-assessment of the effects of treatment with an epidermal growth factor receptor (EGFR) inhibitor on recovery of bladder and locomotor function following thoracic spinal cord injury in rats.

机构信息

Reeve-Irvine Research Center, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA.

出版信息

Exp Neurol. 2012 Feb;233(2):649-59. doi: 10.1016/j.expneurol.2011.04.013. Epub 2011 Nov 10.

Abstract

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat an experiment in which rats that received an inhibitor of the epidermal growth factor receptor (EGFR) exhibited greater sparing/recovery of bladder and motor function and enhanced sparing at the lesion site after contusion injuries at the thoracic level. Young adult female Sprague-Dawley rats received moderate contusions with the NYU impactor (10 g from 12.5 mm, 2 mm rod diameter), and then were implanted with catheters attached to osmotic minipumps for intra-spinal delivery of either PD168393 dissolved in 5% DMSO and HBSS or vehicle alone. Motor function was assessed with the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) and with a grid walk task. Bladder function was assessed by measuring the amount of urine retained in the bladder. Tactile sensitivity was assessed using von Frey hairs and heat and cold sensitivity were assessed by testing hindlimb sensitivity to ethylchloride spray and a hotplate respectively. Rats that received PD168393 were more impaired on motor assessments and also showed greater bladder impairment (larger amounts of retained urine) than rats that received vehicle. These results thus fail to confirm previous studies reporting enhanced recovery following treatment with PD168393.

摘要

这项研究是作为 NIH“卓越研究设施-脊髓损伤”项目的一部分进行的,旨在支持已发表研究的独立复制。在这里,我们重复了一项实验,即在胸段挫伤损伤后,接受表皮生长因子受体 (EGFR) 抑制剂的大鼠表现出更大程度的膀胱和运动功能保留/恢复,以及损伤部位的保留增强。年轻成年雌性 Sprague-Dawley 大鼠接受 NYU 撞击器(12.5 毫米高、2 毫米杆直径,10 克)的中度挫伤,然后植入导管,连接到渗透微型泵,以脊髓内递送溶解在 5% DMSO 和 HBSS 中的 PD168393 或单独的载体。运动功能通过 Basso、Beattie 和 Bresnahan 运动评分量表(BBB)和网格行走任务进行评估。膀胱功能通过测量膀胱中残留的尿液量来评估。触觉敏感性使用 von Frey 毛发进行评估,热和冷敏感性分别通过测试后肢对乙基氯喷雾和热板的敏感性来评估。接受 PD168393 的大鼠在运动评估中受损更严重,并且表现出更大的膀胱损伤(更多的尿液残留),而接受载体的大鼠则没有。因此,这些结果未能证实先前研究报告的 PD168393 治疗后恢复增强的结果。

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