Hwang Misun, Chattaraj Rajarshi, Sridharan Anush, Shin Samuel S, Viaene Angela N, Haddad Sophie, Khrichenko Dmitry, Sehgal Chandra, Lee Daeyeon, Kilbaugh Todd J
Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Neurotrauma Rep. 2022 Feb 22;3(1):97-104. doi: 10.1089/neur.2021.0070. eCollection 2022.
Traumatic brain injury (TBI) is associated with high mortality and morbidity in children and adults. Unfortunately, there is no effective management for TBI in the acute setting. Rodent studies have shown that xenon, a well-known anesthetic gas, can be neuroprotective when administered post-TBI. Gas inhalation therapy, however, the approach typically used for administering xenon, is expensive, inconvenient, and fraught with systemic side effects. Therapeutic delivery to the brain is minimal, with much of the inhaled gas cleared by the lungs. To bridge major gaps in clinical care and enhance cerebral delivery of xenon, this study introduces a novel xenon delivery technique, utilizing microbubbles, in which a high impulse ultrasound signal is used for targeted cerebral release of xenon. Briefly, an ultrasound pulse is applied along the carotid artery at the level of the neck on intravenous injection of xenon microbubbles (XeMBs) resulting in release of xenon from microbubbles into the brain. This delivery technique employs a hand-held, portable ultrasound system that could be adopted in resource-limited environments. Using a high-fidelity porcine model, this study demonstrates the neuroprotective efficacy of xenon microbubbles in TBI for the first time.
创伤性脑损伤（TBI）在儿童和成人中都与高死亡率和高发病率相关。不幸的是，在急性情况下，对于TBI没有有效的治疗方法。啮齿动物研究表明，氙气，一种著名的麻醉气体，在TBI后给药时可具有神经保护作用。然而，气体吸入疗法，即通常用于给予氙气的方法，昂贵、不便且存在许多全身副作用。对大脑的治疗性给药极少，大部分吸入气体被肺部清除。为了弥合临床护理中的重大差距并增强氙气向大脑的递送，本研究引入了一种利用微泡的新型氙气递送技术，其中高脉冲超声信号用于将氙气靶向释放到大脑中。简而言之，在静脉注射氙气微泡（XeMBs）时，沿着颈部水平的颈动脉施加超声脉冲，导致氙气从微泡中释放到大脑中。这种递送技术采用了一种手持式便携式超声系统，可在资源有限的环境中采用。本研究首次使用高保真猪模型证明了氙气微泡在TBI中的神经保护作用。
