1 Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
2 Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, Virginia.
J Neurotrauma. 2019 May 15;36(10):1526-1534. doi: 10.1089/neu.2018.6062. Epub 2019 Jan 25.
Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8 ± 18.3 kPa). Using photoacoustic microscopy (PAM), we quantified changes in cerebral hemodynamics and metabolism-including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen-4 h post-injury. Moreover, we assessed the effect of blast exposure on cerebrovascular reactivity (CVR) to vasodilatory stimulation. With vessel segmentation, we extracted these changes at the single-vessel level, revealing their dependence on vessel type (i.e., artery vs. vein) and diameter. We found that bTBI at this pressure level did not induce pronounced baseline changes in cerebrovascular diameter, blood perfusion, oxygenation, flow, oxygen extraction, and metabolism, except for a slight sO increase in small veins (<45 μm) and blood flow increase in large veins (≥45 μm). In contrast, this blast exposure almost abolished CVR, including arterial dilation, flow upregulation, and venous sO increase. This study is the most comprehensive assessment of cerebrovascular structure and physiology in response to blast exposure to date. The observed impairment in CVR can potentially cause cognitive decline due to the mismatch between cognitive metabolic demands and vessel's ability to dynamically respond to meet the demands. Also, the impaired CVR can lead to increased vulnerability of the brain to metabolic insults, including hypoxia and ischemia.
爆炸创伤性脑损伤（bTBI）是导致与战斗相关的伤亡的主要原因。尽管人们对爆炸引起的神经元和轴突损伤给予了大量关注，但大脑血管，特别是微血管的共存功能障碍仍知之甚少。在这里，我们在 bTBI 的大鼠模型中研究了爆炸引起的脑血管功能障碍（爆炸超压：187.8±18.3kPa）。我们使用光声显微镜（PAM）在损伤后 4 小时定量测量了脑血液动力学和代谢的变化，包括血液灌注、氧合、血流、氧提取分数和氧代谢率。此外，我们评估了爆炸暴露对血管扩张刺激的脑血管反应性（CVR）的影响。通过血管分割，我们在单血管水平上提取了这些变化，揭示了它们对血管类型（即动脉与静脉）和直径的依赖性。我们发现，在这种压力水平下，bTBI 不会引起脑血管直径、血液灌注、氧合、血流、氧提取和代谢的明显基线变化，除了小静脉（<45μm）的 sO 略有增加和大静脉（≥45μm）的血流增加。相比之下，这种爆炸暴露几乎消除了 CVR，包括动脉扩张、血流上调和静脉 sO 增加。这项研究是迄今为止对爆炸暴露后脑血管结构和生理学最全面的评估。观察到的 CVR 受损可能会导致认知能力下降，因为认知代谢需求与血管动态响应以满足需求的能力之间不匹配。此外，受损的 CVR 会导致大脑对代谢损伤（包括缺氧和缺血）的易感性增加。
