Pinzon Alberto, Marcillo Alexander, Quintana Ada, Stamler Sarah, Bunge Mary Bartlett, Bramlett Helen M, Dietrich W Dalton
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14(th) Terrace, LPLC 2-30, Miami, FL 33136, USA.
Brain Res. 2008 Dec 3;1243:146-51. doi: 10.1016/j.brainres.2008.09.047. Epub 2008 Sep 24.
This study was initiated due to an NIH "Facilities of Research--Spinal Cord Injury" contract to support independent replication of published studies that could be considered for a clinical trial in time. Minocycline has been shown to have neuroprotective effects in models of central nervous system injury, including in a contusive spinal cord injury (SCI) model at the thoracic level. Beneficial effects of minocycline treatment included a significant improvement in locomotor behavior and reduced histopathological changes [Lee, S.M., Yune, T.Y., Kim, S.J., Park, D.O.W., Lee, Y.K., Kim, Y.C., Oh, Y.J., Markelonis, G.J., Oh, T.H., 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 20, 1017-1027.] To verify these important observations, we repeated this study in our laboratory. The NYU (MASCIS) Impactor was used to produce a moderate cord lesion at the vertebral level T9-T10 (height 12.5 mm, weight 10 g), (n=45), followed by administration of minocycline, 90 mg/kg (group 1: minocycline IP, n=15; group 2: minocycline IV, n=15; group 3: vehicle IP, n=8; group 4: vehicle IV, n=7) immediately after surgery and followed by two more doses of 45 mg/kg/IP at 12 h and 24 h. Open field locomotion (BBB) and subscores were examined up to 6 weeks after SCI and cords were processed for quantitative histopathological analysis. Administration of minocycline after SCI did not lead to significant behavioral or histopathological improvement. Although positive effects with minocycline have been reported in several animal models of injury with different drug administration schemes, the use of minocycline following contusive SCI requires further investigation before clinical trials are implemented.
本研究是根据美国国立卫生研究院（NIH）的一项“脊髓损伤研究设施”合同发起的，旨在支持对那些有望及时进入临床试验的已发表研究进行独立复制。米诺环素已被证明在中枢神经系统损伤模型中具有神经保护作用，包括在胸段挫伤性脊髓损伤（SCI）模型中。米诺环素治疗的有益效果包括运动行为显著改善以及组织病理学变化减少[Lee, S.M., Yune, T.Y., Kim, S.J., Park, D.O.W., Lee, Y.K., Kim, Y.C., Oh, Y.J., Markelonis, G.J., Oh, T.H., 2003. 米诺环素减少大鼠创伤性脊髓损伤后的细胞死亡并改善功能恢复。《神经创伤杂志》。20, 1017 - 1027。]为了验证这些重要观察结果，我们在实验室中重复了这项研究。使用纽约大学（NYU）（MASCIS）撞击器在T9 - T10椎体水平造成中度脊髓损伤（高度12.5毫米，重量10克），（n = 45），随后在手术后立即给予米诺环素，90毫克/千克（第1组：腹腔注射米诺环素，n = 15；第2组：静脉注射米诺环素，n = 15；第3组：腹腔注射赋形剂，n = 8；第4组：静脉注射赋形剂，n = 7），并在12小时和24小时后再给予两剂45毫克/千克/腹腔注射。在SCI后长达6周的时间里检查旷场运动（BBB）和分项评分，并对脊髓进行定量组织病理学分析。SCI后给予米诺环素并未导致显著的行为或组织病理学改善。尽管在几种不同给药方案的损伤动物模型中已报道米诺环素具有积极作用，但在挫伤性SCI后使用米诺环素在开展临床试验之前还需进一步研究。
