الفهرس 
Free radicals and antioxidantsOnly 14 pages are availabe for public view
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Abstract
In summary, free radicals have been implicated as pathogenic agents in a wide spectrum of human diseases, including diseases associated with premature infants. Loads of ROS , including superoxide anion and nitric oxide, that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Although the majority of evidence supporting these associations is derived from indirect experimental data, the limited amount of clinical data available strengthens the hypothesis. The notion that antioxidant
therapies could be beneficial to disorders mediated by free radicals offers a strong incentive for investigators to fully determine the nature of the association between these highly reactive chemical molecules and disease states. It is highly probable that more than one antioxidant defense system will need to be augmented for such therapeutic strategies to be effective, as different types of free radicals may work in concert to effect cellular injury. However, premature infants are particularly susceptible to free radical-mediated disorders, and therapies designed to combat this mechanism of cell and tissue injury could contribute greatly to improved morbidity and mortality of these vulnerable patients. Recently, specific biomarkers for oxidative damage and antioxidant defense have been introduced into the field of pediatric medicine.
The relationship between free radical production and perinatal brain damage is complex. It is clear that free radical damage results from many pathogenic influences; hypoxia, ischemia-reperfusion, neutrophil and macrophage activation, Fenton chemistry, endothelial cell xanthine oxidase, phospholipid metabolism, NO, mitochondrial oxidative metabolism, iron and proteolytic pathways are all implicated. Reactive oxidant production by these different mechanisms contributes in a piecewise manner to the pathogenesis of perinatal brain injury, but each mechanism is only one of the many factors responsible. There seems to be a maturation-dependent window of vulnerability to free radical attack during oligodendrocyte development. Early in its differentiation, the oligodendrocyte may be vulnerable because of active acquisition of iron for differentiation at a time of relative delay in the development of certain key antioxidant defenses in the brain. Excess free iron and deficient iron-binding and -metabolizing capacity are additional features favoring oxidant stress in premature infants.
Each step in the oxidative cascade has become a potential target for therapy. The multiplicity of pathways and processes involved suggests that there is considerable potential for additive or synergistic benefit from combined therapies. Perinatal HIE is the most common cause of neurologic disease during the neonatal period, and is associated with high mortality and morbidity rate, including CP, mental retardation and seizures. The most acclaimed neuroprotective treatment for infants with HIE to date is early therapeutic hypothermia, starting within 6 hours after hypoxic-ischemic event. Also, PVL is a predominant form of brain injury and leading cause of CP and cognitive deficite in premature infants. The propensity for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. The identification of these cells as susceptible targets in ischemic white matter provides a rationale for the development of preventive therapies aimed at promoting the survival and maturation of oligodendrocyte progenitors. As our understanding of PWMI pathogenesis improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will evolve.