The effectiveness of the anti-CD11 d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage
The effectiveness of the anti-CD11 d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage
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DOI：
10.1016/j.expneurol.2017.06.002
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发表时间：
2017-09-01
影响因子：
5.3
通讯作者：
Brown, A.
中科院分区：
文献类型：
--
作者：
Geremia, N. M.;Hryciw, T.;Brown, A.
我们以前曾报道，管理的CD11 d单克隆抗体（mAb）改善恢复夹压缩模型的SCI。在该模型中，CD11d mAb可减少活化白细胞向受损脊髓的浸润（如脊髓内MPO减少所示）。然而，并非所有的抗炎策略都报告了有益的结果，这表明CD11d mAb治疗的成功可能取决于损伤的类型或严重程度。因此，我们在大鼠颈脊髓半挫伤模型中测试了CD11d mAb治疗。与其在夹压模型中的作用相反，CD11d mAb治疗没有改善前肢功能，也没有显著降低半挫伤脊髓中的MPO水平。为了确定使用CD11d mAb的不同结果是否是由于脊髓损伤的生物力学性质（压迫性SCI与挫伤SO）或损伤的脊柱节段（第12胸椎节段与颈椎节段），我们进一步评估了T12挫伤SO后的CD11d mAb治疗。与T12夹压SCI相比，CD11d mAb治疗没有改善T12挫伤SCI后的运动恢复或显著降低MPO水平。损伤分析显示，与夹压SCI相比，挫伤SCI后出血水平增加。预计伴有椎管内出血增加的SCI对CD11d mAb治疗无效，因为该方法通过完整的血管系统靶向白细胞渗出。这些结果表明，抗CD11d治疗的不同结果在挫伤和夹压模型的SCI是由于不同的病理生理机制，占主导地位的这两种类型的脊髓损伤。皇冠版权所有（C）2017由Elsevier Inc.
We have previously reported that administration of a CD11 d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SO) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SO. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright (C) 2017 Published by Elsevier Inc.