Liska Grant M, Lippert Trenton, Russo Eleonora, Nieves Norton, Borlongan Cesar V
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL.
Cond Med. 2018 Jun;1(4):151-166.
Stroke continues to be an extremely prevalent disease and poses a great challenge in developing safe and effective therapeutic options. Hyperbaric oxygen therapy (HBOT) has demonstrated significant pre-clinical effectiveness for the treatment of acute ischemic stroke, and limited potential in treating chronic neurological deficits. Reported benefits include reductions in oxidative stress, inflammation, neural apoptosis, and improved physiological metrics such as edema and oxygen perfusion, all of which contribute to improved functional recovery. This pre-clinical evidence has failed to translate into an effective evidence-based therapy, however, due in large part to significant inconsistencies in treatment protocols and design of clinical studies. While the medical community works to standardize clinical protocols in an effort to advance HBOT for acute stroke, pre-clinical investigations continue to probe novel applications of HBOT in an effort to optimize stroke neuroprotection. One such promising strategy is HBOT preconditioning. Based upon the premise of mild oxidative stress priming the brain for tolerating the full-blown oxidative stress inherent in stroke, HBOT preconditioning has displayed extensive efficacy. Here, we first review the pre-clinical and clinical evidence supporting HBOT delivery following ischemic stroke and then discuss the scientific basis for HBOT preconditioning as a neuroprotective strategy. Finally, we propose the innovative concept of stem cell preconditioning, in tandem with brain preconditioning, as a promising regenerative pathway for maximizing the application of HBOT for ischemic stroke treatment.
中风仍然是一种极为普遍的疾病，在开发安全有效的治疗方案方面构成了巨大挑战。高压氧疗法（HBOT）在急性缺血性中风的治疗中已显示出显著的临床前有效性，但在治疗慢性神经功能缺损方面潜力有限。报告的益处包括氧化应激、炎症、神经细胞凋亡的减少，以及诸如水肿和氧灌注等生理指标的改善，所有这些都有助于功能恢复的改善。然而，这种临床前证据未能转化为一种有效的循证疗法，这在很大程度上是由于治疗方案和临床研究设计存在显著不一致。当医学界努力规范临床方案以推进HBOT用于急性中风治疗时，临床前研究仍在继续探索HBOT的新应用，以优化中风神经保护。一种这样有前景的策略是HBOT预处理。基于轻度氧化应激使大脑为耐受中风中固有的全面氧化应激做好准备这一前提，HBOT预处理已显示出广泛的疗效。在此，我们首先回顾支持缺血性中风后进行HBOT治疗的临床前和临床证据，然后讨论HBOT预处理作为一种神经保护策略的科学依据。最后，我们提出干细胞预处理与脑预处理相结合的创新概念，作为一种有前景的再生途径，以最大限度地将HBOT应用于缺血性中风治疗。
