Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies.
Much of the damage that occurs in the central nervous system (CNS) following trauma is due to secondary effects of glutamate excitotoxicity, Ca2+ overload, and oxidative stress, three mechanisms that in a spiraling interactive cascade end in neuronal death. Oxidative stress activates mechanisms that result in a neutrophil-mediated inflammation that also causes secondary damage. Mechanisms of oxidative stress are reviewed, with particular attention paid to lipid peroxidation and the central role of reduced glutathione in scavenging peroxides. We suggest that decreasing oxidative stress will greatly reduce the amount of secondary damage due to trauma. Oxidative stress can be minimized by 1) maintaining reduced-glutathione levels through the administration of cysteine precursors such as N-acetylcysteine and 2) limiting neutrophil invasion by administering platelet-activating factor antagonists such as BN 52021. Aggressive nutritional support following CNS trauma can also contribute to maximizing antioxidant defenses. Furthermore, we suggest that flavonoids such as quercetin have the potential to be therapeutically effective because of their free radical quenching, iron chelating, and anti-inflammatory properties.
Juurlink
B H
BH
Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Paterson
P G
PG
D001930:Brain Injuries / Q000188:drug therapy / Q000503:physiopathology*; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D018529:Nutritional Support; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate