Derry Paul J, Vo Anh Tran Tram, Gnanansekaran Aswini, Mitra Joy, Liopo Anton V, Hegde Muralidhar L, Tsai Ah-Lim, Tour James M, Kent Thomas A
Center for Genomics and Precision Medicine, Department of Translational Medical Sciences, Institute of Biosciences and Technology, College of Medicine, Texas A&M Health Science Center, Houston, TX, United States.
Department of Neurosurgery, Center for Neuroregeneration, The Houston Methodist Research Institute, Houston, TX, United States.
Front Cell Neurosci. 2020 Dec 8;14:603043. doi: 10.3389/fncel.2020.603043. eCollection 2020.
Intracerebral hemorrhage (ICH) is a particularly devastating event both because of the direct injury from space-occupying blood to the sequelae of the brain exposed to free blood components from which it is normally protected. Not surprisingly, the usual metabolic and energy pathways are overwhelmed in this situation. In this review article, we detail the complexity of red blood cell degradation, the contribution of eryptosis leading to hemoglobin breakdown into its constituents, the participants in that process, and the points at which injury can be propagated such as elaboration of toxic radicals through the metabolism of the breakdown products. Two prominent products of this breakdown sequence, hemin, and iron, induce a variety of pathologies including free radical damage and DNA breakage, which appear to include events independent from typical oxidative DNA injury. As a result of this confluence of damaging elements, multiple pathways of injury, cell death, and survival are likely engaged including ferroptosis (which may be the same as oxytosis but viewed from a different perspective) and senescence, suggesting that targeting any single cause will likely not be a sufficient strategy to maximally improve outcome. Combination therapies in addition to safe methods to reduce blood burden should be pursued.
脑出血（ICH）是一种极具破坏性的事件，这不仅是因为占位性血液造成的直接损伤，还因为大脑暴露于通常受到保护的游离血液成分所产生的后遗症。不出所料，在这种情况下，通常的代谢和能量途径不堪重负。在这篇综述文章中，我们详细阐述了红细胞降解的复杂性、红细胞凋亡导致血红蛋白分解为其组成成分的过程、该过程中的参与因素，以及损伤可能传播的节点，例如通过分解产物的代谢产生有毒自由基。这个分解序列的两个主要产物，血红素和铁，会引发多种病理变化，包括自由基损伤和DNA断裂，其中似乎包括一些独立于典型氧化性DNA损伤的事件。由于这些损伤因素的共同作用，可能会启动多种损伤、细胞死亡和存活途径，包括铁死亡（可能与氧化应激相同，但从不同角度来看）和衰老，这表明针对任何单一病因可能都不是最大限度改善预后的充分策略。除了采用安全方法减轻血液负担外，还应寻求联合治疗。
