Oxidative Stress in the Early Phase of Traumatic Central Nervous System Injury: Clinical Data
Cerebrovascular and metabolic changes associated with traumatic injury to the CNS may be related, in part, with pathological alterations in the intracellular neurochemical system. These events may include alterations in neurotransmitter synthesis and release or changes in pre/or postsynaptic receptor activity. Other changes may include alterations in the synthesis and activity of endogenous neuroprotective compounds (e. g. enzymatic and non-enzymatic antioxidant) or pathological expression and release of endogenous “autodestructive” compounds associated with inflammation and/or with alterated oxidative metabohsm (e. g. free radicals). Although the timing of the precise cascade of neurochemical events following traumatic brain injury is poorly understood, there is now extensive experimental support for early occurrence and pathological importance of oxygen radical species (ROS) formation and cell membrane lipid peroxidation (LP) (1-4). The potential sources of oxygen radicals within the brain after trauma insult include the arachidonic acid cascade, catecholamine oxidation, electron “leakage” from the mitochondrial electron transfer chain, oxidation of extravasated hemoglobin and later infiltrating neutrophils (Figs. 1, 2). The radical dependent lipid peroxidation of nervous and vascular cell membranes and myelin is catalyzed by free iron released from hemoglobin, transferrin and ferritin by either lowered tissue pH or oxygen radicals. The LP is a geometrically progressing process that spreads over the surface of the cell membrane causing impairment to phospholipid-dependent enzymes, disruption of ionic gradients, membrane lysis and cell death. Criteria for the establishment of the pathophysiological significance of oxygen radical reactions include: a) the demonstration of increased post-traumatic levels of oxygen radicals and lipid peroxides after CNS trauma; b) the spatial and temporal correlation between oxygen radical formation and physiological and pathological alterations (e. g. decrease of oxygen consumption, energy failure, loss of microvasculature regulation, edema and progressive post-traumatic ischemia development); and c) a striking similarity between post-traumatic CNS pathology and experimental chemical peroxidative insult (e. g. ironmicroinjection).
KeywordsJugular Bulb Experimental Spinal Cord Injury Traumatic Central Nervous System Oxygen Radical Formation Mitochondrial Electron Transfer Chain
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