Puniak M A, Freeman G M, Agresta C A, Van Newkirk L, Barone C A, Salzman S K
Alfred I. duPont Institute, Spinal Trauma Research Program, Wilmington, Delaware.
J Neurotrauma. 1991 Fall;8(3):193-203. doi: 10.1089/neu.1991.8.193.
The therapeutic efficacies of a serotonin antagonist (mianserin), an opioid antagonist (nalmefene), and a TRH analog (YM-14673) were compared in a well-characterized model of experimental spinal trauma in the rat. Injury was produced by the weight-drop method at T10 and confirmed by the disappearance of the somatosensory evoked response during the subsequent 15 minutes. Drug or vehicle treatments were administered randomly as a single intravenous bolus 15 minutes after injury. Functional outcome was blindly assessed for 2 weeks postinjury using a modified Tarlov scale and the Rivlin-Tator angleboard test. The survival of descending raphe-spinal axons was determined by measurement of serotonin in postmortem spinal tissues located above and below the injury, and histopathologic studies were carried out at the site of injury. All agents displayed similar and significant efficacies with respect to Tarlov and Rivlin-Tator measures of motor recovery and preservation of raphe-spinal fibers below the lesion site. In contrast, none of the agents were effective for preserving the central gray matter or myelin staining in the white matter in slices of tissue from the site of injury. Results are discussed in terms of the early treatment of spinal cord injury and future clinical trials.
在一个特征明确的大鼠实验性脊髓损伤模型中，比较了一种5-羟色胺拮抗剂（米安色林）、一种阿片类拮抗剂（纳美芬）和一种促甲状腺激素释放激素类似物（YM-14673）的治疗效果。通过T10节段的重物坠落法造成损伤，并通过随后15分钟体感诱发电位的消失来确认。损伤后15分钟，将药物或赋形剂治疗随机作为单次静脉推注给药。使用改良的塔尔洛夫量表和里夫林-塔托角板试验对损伤后2周的功能结果进行盲法评估。通过测量损伤部位上方和下方死后脊髓组织中的5-羟色胺来确定下行中缝脊髓轴突的存活情况，并在损伤部位进行组织病理学研究。就塔尔洛夫和里夫林-塔托运动恢复测量以及损伤部位以下中缝脊髓纤维的保留而言，所有药物均显示出相似且显著的疗效。相比之下，没有一种药物对保留损伤部位组织切片中白质的中央灰质或髓鞘染色有效。根据脊髓损伤的早期治疗和未来的临床试验对结果进行了讨论。
