Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy
Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy
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DOI：
10.1172/jci.insight.92512
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发表时间：
2017-06-02
期刊：
影响因子：
8
通讯作者：
Fehlings, Michael G.
中科院分区：
文献类型：
--
作者：
Vidal, Pia M.;Karadimas, Spyridon K.;Fehlings, Michael G.
退行性脊髓型颈椎病是最常见的进行性非创伤性脊髓损伤。最常见的推荐治疗是手术减压，尽管干预的最佳时机是一个正在争论的领域。本研究的主要目的是评估延迟减压是否会影响缺血再灌注损伤的程度并改变DCM的预后轨迹。通过DCM小鼠模型，我们发现减压会导致脊髓内炎症细胞因子水平增加1.5至2倍。延迟减压与加重的再灌注损伤、星形胶质增生和较差的神经恢复有关。此外，延迟减压与炎症细胞因子的延长升高和外周单核细胞炎症反应加剧相关（P < 0.01和0.001）。相比之下，早期减压导致再灌注介导的炎症消退，神经系统改善，痛觉过敏减轻。在CSM AOSpine北美和国际研究的受试者中也观察到类似的发现，与早期干预的患者相比，延迟减压手术导致的神经系统改善较差。我们的数据表明，延迟DCM手术减压会加重再灌注损伤，并与细胞因子表达、小胶质细胞激活和星形胶质细胞增生水平的持续升高有关，并与较差的神经恢复有关。
Degenerative cervical myelopathy (DCM) is the most common progressive nontraumatic spinal cord injury. The most common recommended treatment is surgical decompression, although the optimal timing of intervention is an area of ongoing debate. The primary objective of this study was to assess whether a delay in decompression could influence the extent of ischemia-reperfusion injury and alter the trajectory of outcome in DCM. Using a DCM mouse model, we show that decompression acutely led to a 1.5- to 2-fold increase in levels of inflammatory cytokines within the spinal cord. Delayed decompression was associated with exacerbated reperfusion injury, astrogliosis, and poorer neurological recovery. Additionally, delayed decompression was associated with prolonged elevation of inflammatory cytokines and an exacerbated peripheral monocytic inflammatory response (P < 0.01 and 0.001). In contrast, early decompression led to resolution of reperfusion-mediated inflammation, neurological improvement, and reduced hyperalgesia. Similar findings were observed in subjects from the CSM AOSpine North America and International studies, where delayed decompressive surgery resulted in poorer neurological improvement compared with patients with an earlier intervention. Our data demonstrate that delayed surgical decompression for DCM exacerbates reperfusion injury and is associated with ongoing enhanced levels of cytokine expression, microglia activation, and astrogliosis, and paralleled with poorer neurological recovery.