Baucom Matthew R, Wallen Taylor E, Singer Kathleen E, Youngs Jackie, Schuster Rebecca M, Blakeman Thomas C, McGuire Jennifer L, Strilka Richard, Goodman Michael D
Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio.
J Surg Res. 2022 Nov;279:352-360. doi: 10.1016/j.jss.2022.05.019. Epub 2022 Jul 8.
Early aeromedical evacuation after traumatic brain injury (TBI) has been associated with worse neurologic outcomes in murine studies and military populations. The goal of this study was to determine if commonly utilized medications, including allopurinol, propranolol, or tranexamic acid (TXA), could mitigate the secondary traumatic brain injury experienced during the hypobaric and hypoxic environment of aeromedical evacuation.
Porcine TBI was induced via controlled cortical injury. Twenty nonsurvival pigs were separated into four groups (n = 5 each): TBI+25 mL normal saline (NS), TBI+4 mg propranolol, TBI+100 mg allopurinol, and TBI+1g TXA. The pigs then underwent simulated AE to an altitude of 8000 ft for 4 h with an SpO of 82-85% and were sacrificed 4 h later. Hemodynamics, serum cytokines, and hippocampal p-tau accumulation were assessed. An additional survival cohort was partially completed with TBI/NS (n = 5), TBI/propranolol (n = 2) and TBI/allopurinol groups (n = 2) survived to postinjury day 7.
There were no significant differences in hemodynamics, tissue oxygenation, cerebral blood flow, or physiologic markers between treatment groups and saline controls. Transient differences in IL-1b and IL-6 were noted but did not persist. Neurological Severity Score (NSS) was significantly lower in the TBI + allopurinol group on POD one compared to NS and propranolol groups. P-tau accumulation was decreased in the nonsurvival animals treated with allopurinol and TXA compared to the TBI/NS group.
Allopurinol, propranolol, and TXA, following TBI, do not induce adverse changes in systemic or cerebral hemodynamics during or after a simulated postinjury flight. While transient changes were noted in systemic cytokines and p-tau accumulation, further investigation will be needed to determine any persistent neurological effects of injury, flight, and pharmacologic treatment.
在小鼠研究和军事人群中，创伤性脑损伤（TBI）后早期航空医疗后送与更差的神经学预后相关。本研究的目的是确定常用药物，包括别嘌醇、普萘洛尔或氨甲环酸（TXA），是否可以减轻航空医疗后送的低压和低氧环境中经历的继发性创伤性脑损伤。
通过控制性皮质损伤诱导猪TBI。20只非存活猪被分为四组（每组n = 5）：TBI+25 mL生理盐水（NS）、TBI+4 mg普萘洛尔、TBI+100 mg别嘌醇和TBI+1 g TXA。然后将猪模拟航空医疗后送到8000英尺高度4小时，使血氧饱和度（SpO）维持在82 - 85%，4小时后处死。评估血流动力学、血清细胞因子和海马p - tau蛋白积累情况。另外一个存活队列部分完成，TBI/NS组（n = 5）、TBI/普萘洛尔组（n = 2）和TBI/别嘌醇组（n = 2）存活至伤后第7天。
治疗组与生理盐水对照组在血流动力学、组织氧合、脑血流量或生理指标方面无显著差异。观察到白细胞介素-1β（IL-1b）和白细胞介素-6（IL-6）有短暂差异，但未持续存在。与NS组和普萘洛尔组相比，TBI +别嘌醇组在伤后第1天的神经严重程度评分（NSS）显著更低。与TBI/NS组相比，用别嘌醇和TXA治疗的非存活动物中p - tau蛋白积累减少。
TBI后，别嘌醇、普萘洛尔和TXA在模拟伤后飞行期间或之后不会引起全身或脑血流动力学的不良变化。虽然在全身细胞因子和p - tau蛋白积累方面观察到短暂变化，但需要进一步研究以确定损伤、飞行和药物治疗的任何持续性神经学影响。
