Variants of the endothelial nitric oxide gene and cerebral blood flow after severe traumatic brain injury.
Variants of the endothelial nitric oxide gene and cerebral blood flow after severe traumatic brain injury.
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DOI：
10.1089/neu.2010.1476
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发表时间：
2011-05
影响因子：
4.2
通讯作者：
C. Robertson;S. Gopinath;A. Valadka;M. Van;P. Swank;J. Goodman
中科院分区：
文献类型：
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作者：
C. Robertson;S. Gopinath;A. Valadka;M. Van;P. Swank;J. Goodman
实验研究表明，内皮型一氧化氮合酶（NOS 3）产生的一氧化氮在脑外伤（TBI）后维持脑血流量（CBF）方面发挥作用。本研究的目的是确定NOS 3基因的常见变异是否有助于严重TBI后的低灌注。研究了51例严重TBI患者。脑血流动力学，包括全球CBF的稳定氙计算机断层扫描（CT）技术，颈内动脉流量（ICA-FEVER），和颅内血管的流速，在受伤后12小时内，并在48小时后受伤。收集血液样品用于DNA分析，并进行以下NOS 3基因变体的基因分型：-786 T>C、894 G>T和27 bp VNTR。脑血流动力学与-786T>C基因型关系最为密切。正常T/T基因型的CBF平均为57.7±3.0 mL/100 g/min，T/C基因型为47.0±2.5 mL/100 g/min，C/C基因型为37.3±8.8 mL/100 g/min（p=0.0146）。脑血管阻力遵循相反的模式，最高值发生在C/C基因型（p=0.0027）。在C/C基因型患者损伤较重的半球中，在损伤后12小时发现最低的ICA-FcR为124±43 mL/min（p=0.0085）。T/T基因型患者的死亡率为20%，T/C基因型患者的死亡率为17%。与此相反，两个C/C基因型患者在伤后6个月死亡（p=0.022）。这项研究的结果支持了NO产生的NOS 3活性在维持脑外伤后CBF的重要性，因为在具有-786C等位基因的患者中发现了较低的CBF值。这项研究表明，患者的个体基因组成可能有助于大脑对损伤的反应，并决定患者在损伤中幸存的机会。这里的结果将需要在更多的患者中进行研究，但可以解释严重TBI后发生的结果的一些变异性。
Experimental studies suggest that nitric oxide produced by endothelial nitric oxide synthase (NOS3) plays a role in maintaining cerebral blood flow (CBF) after traumatic brain injury (TBI). The purpose of this study was to determine if common variants of the NOS3 gene contribute to hypoperfusion after severe TBI. Fifty-one patients with severe TBI were studied. Cerebral hemodynamics, including global CBF by the stable xenon computed tomography (CT) technique, internal carotid artery flow volume (ICA-FVol), and flow velocity in intracranial vessels, were measured within 12 h of injury, and at 48 h after injury. A blood sample was collected for DNA analysis, and genotyping of the following variants of the NOS3 gene was performed: -786T>C, 894G>T, and 27bp VNTR. Cerebral hemodynamics were most closely related to the-786T>C genotype. CBF averaged 57.7±3.0 mL/100 g/min with the normal T/T genotype, 47.0±2.5 mL/100 g/min with the T/C, and 37.3±8.8 mL/100 g/min with the C/C genotype (p=0.0146). Cerebrovascular resistance followed an inverse pattern with the highest values occurring with the C/C genotype (p=0.0027). The lowest ICA-FVol of 124±43 mL/min was found at 12 h post-injury in the more injured hemisphere of the patients with the C/C genotype (p=0.0085). The mortality rate was 20% in patients with the T/T genotype and 17% with the T/C genotype. In contrast, both of the patients with the C/C genotype were dead at 6 months post-injury (p=0.022). The findings in this study support the importance of NO produced by NOS3 activity in maintaining CBF after TBI, since lower CBF values were found in patients having the -786C allele. The study suggests that a patient's individual genetic makeup may contribute to the brain's response to injury and determine the patient's chances of surviving the injury. The results here will need to be studied in a larger number of patients, but could explain some of the variability in outcome that occurs following severe TBI.