Neurocritical care monitoring correlates with neuropathology in a swine model of pediatric traumatic brain injury.
Neurocritical care monitoring correlates with neuropathology in a swine model of pediatric traumatic brain injury.
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DOI：
10.1227/neu.0b013e3182284aa1
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发表时间：
2011-11
期刊：
影响因子：
4.8
通讯作者：
Margulies SS
中科院分区：
文献类型：
--
作者：
Friess SH;Ralston J;Eucker SA;Helfaer MA;Smith C;Margulies SS
小动物模型已被用于创伤性脑损伤（TBI）的研究，以探讨TBI的基本机制和病理。不幸的是，在小动物模型中成功的TBI研究并没有导致TBI患者临床结果的显著改善。开发一种临床相关的未成熟的大型动物模型，用于TBI后的儿科神经重症监护。将11只4周龄仔猪随机分配至无冲击的快速轴向头部旋转组（N=6）或内固定假手术组（N=5）。所有动物均在额叶放置颅内压监测仪、脑组织氧（PbtO 2）探头和脑微透析探头，并在损伤后6 h收集数据。与假手术组相比，受伤动物的颅内压和乳酸-丙酮酸比（LPR）持续升高，PbtO 2降低。PbtO 2和LPR从单独的额叶有很强的线性相关性，在假手术和受伤的动物。神经病理学检查表明，在损伤后6小时，与假手术相比，损伤动物中存在显著的轴突损伤和梗死体积。随着时间的推移，受伤和假手术动物的PbtO 2与总损伤体积呈强负相关。平均LPR与总损伤量有很强的相关性。LPR和PbtO 2可用作我们的神经病理学损伤模型中的一系列非末端二级标记物，并可用作急性损伤后新干预和治疗的评价指标。这种转化模型弥补了小动物模型中TBI研究与儿科TBI人群临床试验之间的重要知识差距。
Small animal models have been used in traumatic brain injury (TBI) research to investigate the basic mechanisms and pathology of TBI. Unfortunately, successful TBI investigations in small animal models have not resulted in marked improvements in clinical outcomes of TBI patients. To develop a clinically relevant immature large animal model of pediatric neurocritical care following TBI. Eleven 4 week old piglets were randomized to either rapid axial head rotation without impact (N=6) or instrumented sham (N=5). All animals had an intracranial pressure monitor, brain tissue oxygen (PbtO2) probe, and cerebral microdialysis probe placed in the frontal lobe and data collected for 6 h following injury. Injured animals had sustained elevations in intracranial pressure and lactate-pyruvate ratio (LPR), and decreased PbtO2 compared to sham. PbtO2 and LPR from separate frontal lobes had strong linear correlation in both sham and injured animals. Neuropathologic examination demonstrated significant axonal injury and infarct volumes in injured animals compared to sham at 6 hours post-injury. Averaged over time, PbtO2 in both injured and sham animals had a strong inverse correlation with total injury volume. Average LPR had a strong correlation with total injury volume. LPR and PbtO2 can be utilized as serial non-terminal secondary markers in our injury model for neuropathology, and as evaluation metrics for novel interventions and therapeutics in the acute post-injury period. This translational model bridges a vital gap in knowledge between TBI studies in small animal models and clinical trials in the pediatric TBI population.