Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats
Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats
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DOI：
10.1016/j.neulet.2013.08.048
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发表时间：
2013-10-25
影响因子：
2.5
通讯作者：
Gutierrez-Ospina, G.
中科院分区：
文献类型：
--
作者：
Ibarra, A.;Sosa, M.;Gutierrez-Ospina, G.
医源性脊髓损伤是脊柱手术常见的并发症。为了尝试建立一种预防性治疗预期的SC损伤，我们测试了单剂量（SD）疫苗与在SC挫伤前添加加强剂量（BD）的神经源性肽（A91）的效果。在SC损伤后立即用A91免疫已证明诱导显著的组织保护和运动恢复。损伤后，只有BD疫苗接种时间表有神经保护作用。它能够改善神经恢复，其总是显著高于在SD免疫的大鼠或仅用PBS处理的大鼠中观察到的神经恢复。在研究结束时，用A91 BD处理的动物呈现9.75+/-0.17（平均标准偏差）的BBB评分，而用SD或PBS处理的大鼠分别具有6.6+/-0.7和5.6+/-0.6的评分。在下一步中，我们试图证实A91免疫诱导的神经保护作用。为此，我们评估了SC损伤后60天红核脊髓神经元（RSN）和腹角神经元（VHN）的存活情况。BD疫苗接种诱导RSN和VHN在损伤后的显著存活。最后，该疗法的失败或成功（分别为SD或BD）与较低（SD）或较高（BD）的A91特异性T细胞增殖相关。预防性神经保护与初始和随后的加强剂量的A91可以改善恢复后SC损伤持续在侵入性脊柱手术程序。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75+/-0.17 (mean standard deviation) while rats treated with SD or PBS had a score of 6.6+/-0.7 and 5.6+/-0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures. (C) 2013 Elsevier Ireland Ltd. All rights reserved.