Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans
Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans
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DOI：
10.1126/scitranslmed.3009430
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发表时间：
2014-10-01
影响因子：
17.1
通讯作者：
Okada, Seiji
中科院分区：
文献类型：
--
作者：
Kobayakawa, Kazu;Kumamaru, Hiromi;Okada, Seiji
脊髓损伤（SCI）是一种破坏性疾病，其加重因素的识别是迫切需要的。我们证明，短暂的高血糖症在急性SCI是一个有害因素，损害功能改善小鼠和人类患者急性SCI后。在体内和体外高血糖条件下，炎症通过促进小胶质细胞中核因子κ B（NF-κ B）转录因子的核转位而增强。在急性SCI期间，高血糖小鼠表现出进行性神经损伤，与血糖正常小鼠相比，运动障碍更严重。与动物研究结果一致，对528例SCI患者数据的Pearson卡方检验（2）分析表明，入院时高血糖（血糖浓度≥ 126 mg/dl）是功能预后不良的重要风险预测因子。此外，多元线性回归分析显示，入院时的高血糖是运动预后不良的一个强有力的独立危险因素，即使排除了糖尿病伴慢性高血糖的患者（回归系数，-1.37; 95%可信区间，-2.65至-0.10; P < 0.05）。在高血糖小鼠急性SCI期间控制血糖挽救了病理生理学的恶化并改善了运动功能结果。我们的研究结果表明，急性SCI期间的高血糖可能是一个有用的预后因素，对运动功能有负面影响，强调了中枢神经系统损伤后实现严格血糖控制的重要性。
Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kappa B (NF-kappa B) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson chi(2) analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration >= 126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, -1.37; 95% confidence interval, -2.65 to -0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.