Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurotrauma. 2011 May;28(5):727-37. doi: 10.1089/neu.2010.1476. Epub 2011 May 4.
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.
实验研究表明，内皮型一氧化氮合酶（NOS3）产生的一氧化氮在创伤性脑损伤（TBI）后维持脑血流（CBF）中发挥作用。本研究的目的是确定 NOS3 基因的常见变体是否导致严重 TBI 后的低灌注。研究了 51 例严重 TBI 患者。通过稳定氙气计算机断层扫描（CT）技术测量脑血流动力学，包括全局 CBF、颈内动脉血流容积（ICA-FVol）和颅内血管血流速度，在损伤后 12 小时内和损伤后 48 小时进行测量。采集血样进行 DNA 分析，并对 NOS3 基因的以下变体进行基因分型：-786T>C、894G>T 和 27bpVNTR。脑血流动力学与-786T>C 基因型最密切相关。正常 T/T 基因型时 CBF 平均为 57.7±3.0mL/100g/min，T/C 基因型时为 47.0±2.5mL/100g/min，C/C 基因型时为 37.3±8.8mL/100g/min（p=0.0146）。脑血管阻力呈相反模式，C/C 基因型时最高（p=0.0027）。在损伤后 12 小时，C/C 基因型患者患侧半球的 ICA-FVol 最低，为 124±43mL/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%。相比之下，C/C 基因型的两位患者在损伤后 6 个月时均死亡（p=0.022）。本研究结果支持 NOS3 活性产生的 NO 在 TBI 后维持 CBF 的重要性，因为在携带-786C 等位基因的患者中发现 CBF 值较低。该研究表明，患者的个体遗传构成可能会影响大脑对损伤的反应，并决定患者存活损伤的机会。需要在更多患者中研究这些结果，但可以解释严重 TBI 后发生的一些结果变异性。
