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  3. The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis

The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis

  • Front Cell Neurosci. 2020 Dec 8:14:603043. doi: 10.3389/fncel.2020.603043.
Paul J Derry 1,  Anh Tran Tram Vo 1,  Aswini Gnanansekaran 1,  Joy Mitra 2,  Anton V Liopo 1,  Muralidhar L Hegde 2,  Ah-Lim Tsai 3,  James M Tour 4 5 6,  Thomas A Kent 1 4 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Neurosurgery, Center for Neuroregeneration, The Houston Methodist Research Institute, Houston, TX, United States.
  • 3 Division of Hematology, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States.
  • 4 Department of Chemistry, Rice University, Houston, TX, United States.
  • 5 Department of Computer Science, George R. Brown School of Engineering, Rice University, Houston, TX, United States.
  • 6 Department of Materials Science and NanoEngineering, George R. Brown School of Engineering, Rice University, Houston, TX, United States.
  • 7 Stanley H. Appel Department of Neurology, Institute for Academic Medicine, Houston Methodist Hospital, Houston, TX, United States.
PMID: 33363457 DOI: 10.3389/fncel.2020.603043
Abstract

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.

Keywords

ferroptosis; hemoglobin; intracerebral hemorrhage; iron; oxytosis; reactive oxygen species; senescence.

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