Camara Richard, Matei Nathanael, Camara Justin, Enkhjargal Budbazar, Tang Jiping, Zhang John H
Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
Department of Physiology and Pharmacology; Department of Anesthesiology; Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.
Med Gas Res. 2019 Apr-Jun;9(2):74-79. doi: 10.4103/2045-9912.260648.
The high morbidity, high mortality, and significant shortage of effective therapies for subarachnoid hemorrhage (SAH) have created an urgency to discover novel therapies. Human studies in Asia have established the safety of hydrogen gas in the treatment of hepatic, renal, pulmonary, and cardiac diseases. Mechanistically, hydrogen gas has been shown to affect oxidative stress, inflammation, and apoptosis. We hypothesized that hydrogen therapy would improve neurological function and increase survival rate in SAH. High dose hydrogen gas (66% at 3 L/min) was administered for 2 hours at 0.5, 8, and 18 hours after SAH. This treatment increased 72-hour survival rate and provided 24-hour neuroprotection after SAH in rats. To our knowledge, this is the first report demonstrating that high dose hydrogen gas therapy reduces mortality and improves outcome after SAH. Our results correlate well with the proposed mechanisms of hydrogen gas therapy within the literature. We outline four pathways and downstream targets of hydrogen gas potentially responsible for our results. A potentially complex network of pathways responsible for the efficacy of hydrogen gas therapy, along with a limited mechanistic understanding of these pathways, justifies further investigation to provide a basis for clinical trials and the advancement of hydrogen gas therapy in humans. This study was approved by the Institutional Animal Care and Use Committee of Loma Linda University, USA (Approval No. 8160016) in May 2016.
蛛网膜下腔出血(SAH)的高发病率、高死亡率以及有效治疗方法的严重短缺促使人们迫切需要发现新的治疗方法。亚洲的人体研究已证实氢气在治疗肝脏、肾脏、肺部和心脏疾病方面的安全性。从机制上讲,氢气已被证明会影响氧化应激、炎症和细胞凋亡。我们假设氢气疗法可改善SAH患者的神经功能并提高生存率。在SAH后的0.5、8和18小时,以3升/分钟的流量给予高剂量氢气(66%)2小时。该治疗提高了大鼠SAH后的72小时生存率,并提供了24小时的神经保护作用。据我们所知,这是第一份证明高剂量氢气疗法可降低SAH死亡率并改善预后的报告。我们的结果与文献中提出的氢气疗法机制高度相关。我们概述了可能导致我们研究结果的氢气的四条作用途径和下游靶点。负责氢气疗法疗效的潜在复杂途径网络,以及对这些途径的有限机制理解,证明有必要进一步研究,为临床试验和人类氢气疗法的发展提供依据。本研究于2016年5月获得美国洛马林达大学机构动物护理和使用委员会批准(批准号8160016)。