All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga­ nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be­ come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti­ tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere­ brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1981.18

Cell Damage in the Brain: A Speculative Synthesis

Oxygen is indispensable for aerobic organisms including, of course, human beings, but it is believed that oxygen also may be responsible for undesired phenomena. In particular, oxygen species such as hydrogen peroxide, superoxide radical anion, and singlet oxygen are proposed as agents attacking polyunsaturated fatty acids in cell membranes, giving rise to lipid peroxidation. Several reports have suggested that lipid peroxidation may result in destabilization and disintegration of cell membranes, leading to liver injury and other diseases, and finally, to aging and susceptibility to cancer (4).

Antioxidants/antimutagens in food.

The products of oxygen reduction (superoxide anion, hydrogen peroxide, hydroxyl radicals) and excitation (singlet oxygen) have been implicated in the toxic properties of phagocytes (neutrophils, eosinophils, and mononuclear phagocytes). Enzymes that potentiate (such as peroxidase) or limit (such as catalase, superoxide dismutase) the toxicity of these agents contribute to the complexity of the oxygen-dependent antimicrobial systems of phagocytes. These toxic systems are dormant when the phagocyte is at rest but are activated when the need arises and directed to the destruction of invading microorganisms and other foreign cells. Occasionally, the toxic systems are directed against normal host cells and in this way contribute to the pathogenesis of disease.

Oxygen metabolism and the toxic properties of phagocytes.

The antioxidant role of vitamin C

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2885%2981208-4

Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. The important contribution made by plasma proteins.

Irwin Fridovich

Papers

CHAPTER 6 – Oxygen Radicals, Hydrogen Peroxide, and Oxygen Toxicity