Normoxic ventilatory resuscitation following controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus - Laboratory investigation
Normoxic ventilatory resuscitation following controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus - Laboratory investigation
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DOI：
10.3171/jns/2008/108/01/0124
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Fiskum, Gary
中科院分区：
文献类型：
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作者：
Ahn, Edward S.;Robertson, Courtney L.;Fiskum, Gary
物体。重型颅脑损伤(TBI)后用100%氧气进行机械复苏引起了人们对活性氧(ROS)生成增加的担忧。过氧亚硝酸根参与酪氨酸残基硝化的产物3-硝基酪氨酸(3-NT)是蛋白质氧化损伤的标志。作者推测，与常氧复苏(21%FiO(2)浓度)相比，高氧复苏(100%吸入氧[FiO(2)]浓度)可导致ROS诱导的蛋白质损伤增加。雄性SD大鼠采用控制性皮质撞击伤(CCI)并复苏，分别采用常氧或高氧通气1h(每组5只)。伤后24小时取脑，用3-NT免疫组织化学方法检测大鼠海马区。在第二个实验中，动物同样接受CCI损伤和常氧或高氧1小时(每组4只大鼠)。伤后1周进行神经元核团免疫组织化学染色，进行神经元计数。高氧组大鼠海马区3-NT染色明显增强。与高氧组相比，常氧组CA1区染色减少51.0%，CA3区染色减少50.8%(p<；0.05，这两个区域均为P<；0.05)。损伤常氧组与假手术对照组比较，染色差异无统计学意义。在神经元存活延迟分析(神经元计数)中，高氧组和常氧组之间无显著差异。在这一临床相关的脑外伤模型中，与高氧复苏相比，常氧复苏显著减少了蛋白质的氧化损伤。高氧复苏对神经细胞计数没有好处。这些发现表明，重型颅脑损伤后早期高氧通气可能会加剧蛋白质的氧化损伤。
Object. Ventilatory resuscitation with 100% O-2 after severe traumatic brain injury (TBI) raises concerns about the increased production of reactive oxygen species (ROS). The product of peroxynitrite-meditated tyrosine residue nitration, 3-nitrotyrosine (3-NT), is a marker for oxidative damage to proteins. The authors hypothesized that posttraumatic resuscitation with hyperoxia (100% fraction of inspired oxygen [FiO(2)] concentration) results in increased ROS-induced damage to proteins compared with resuscitation using normoxia (21% FiO(2) concentration).Methods. Male Sprague-Dawley rats underwent controlled cortical impact (CCI) injury and resuscitation with either normoxic or hyperoxic ventilation for I hour (5 rats per group). Twenty-four hours after injury, rat hippocampi were evaluated using 3-NT immunostaining. In a second experiment, animals similarly underwent CCI injury and normoxic or hyperoxic ventilation for 1 hour (4 rats per group). One week after injury, neuronal counts were performed after neuronal nuclei immunostaining.Results. The 3-NT staining was significantly increased in the hippocampi of the hyperoxic group. The normoxic group showed a 51.0% reduction of staining in the CA1 region compared with the hyperoxic group and a 50.8% reduction in the CA3 region (p < 0.05, both regions). There was no significant difference in staining between the injured normoxic group and sham-operated control groups. In the delayed analysis of neuronal survival (neuronal counts), there was no significant difference between the hyperoxic and normoxic groups.Conclusions. In this clinically relevant model of TBI, normoxic resuscitation significantly reduced oxidative damage to proteins compared with hyperoxic resuscitation. Neuronal counts showed no benefit from hyperoxic resuscitation. These findings indicate that hyperoxic ventilation in the early stages after severe TBI may exacerbate oxidative damage to proteins.