Acute rolipram/thalidomide treatment improves tissue sparing and locomotion after experimental spinal cord injury
Acute rolipram/thalidomide treatment improves tissue sparing and locomotion after experimental spinal cord injury
复制标题
DOI：
10.1016/j.expneurol.2009.01.005
复制
发表时间：
2009-04-01
影响因子：
5.3
通讯作者：
Brook, Gary A.
中科院分区：
文献类型：
--
作者：
Koopmans, Guido C.;Deumens, Ronald;Brook, Gary A.
创伤性脊髓损伤(SCI)由于原发的机械性损伤和继发的组织变性导致严重的和永久性的功能缺陷。一连串的继发性退变事件构成了一系列的治疗靶点，如果治疗成功，可以显著改善创伤性脊髓损伤后的功能丧失。在损伤后的早期几个小时，强大的促炎细胞因子，包括肿瘤坏死因子α(TNF-α)和白介素1β(IL-1β)被合成并释放，在继发性组织退变中发挥关键作用。在本研究中，FDA批准的药物罗利普兰和沙利度胺在脊髓挫伤的实验模型上评估了其减少继发性组织变性和改善运动功能的能力。两种药物联合急性单次腹腔给药可减少肿瘤坏死因子-α和白介素1-β的产生，并改善病变中心白质的保留。伴随而来的是6周后BBB运动评分的显著改善(2.6分)。目前，没有一种被广泛接受的干预策略适用于人类脊髓损伤的早期治疗。目前的数据表明，罗利普兰和沙利度胺急性联合应用的临床试验可能是合理的。使用这种“已确定的药物”可以促进尽早开始试验。(C)2009 Elsevier Inc.保留所有权利。
Traumatic spinal cord injury (SCI) causes severe and permanent functional deficits due to the primary mechanical insult followed by secondary tissue degeneration. The cascade of secondary degenerative events constitutes a range of therapeutic targets which, if successfully treated, could significantly ameliorate functional loss after traumatic SCI. During the early hours after injury, potent pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are synthesized and released, playing key roles in secondary tissue degeneration. In the present investigation, the ability of rolipram and thalidomide (FDA approved drugs) to reduce secondary tissue degeneration and improve motor function was assessed in an experimental model of spinal cord contusion injury. The combined acute single intraperitoneal administration of both drugs attenuated TNF-alpha and IL-1 beta production and improved white matter Sparing at the lesion epicenter. This was accompanied by a significant (2.6 point) improvement in the BBB locomotor score by 6 weeks. There is, at present, no widely accepted intervention strategy that is appropriate for the early treatment of human SCI. The present data suggest that clinical trials for the acute combined application of rolipram and thalidomide may be warranted. The use of such "established drugs" could facilitate the early initiation of trials. (C) 2009 Elsevier Inc. All rights reserved.