[Neuroprotection. Models and basic principles].
This review describes recently recognized pathophysiologic mechanisms responsible for brain damage during ischemia and reperfusion and new therapeutic concepts developed on a rational basis. Mediators of secondary damage include excitotoxins such as glutamate, acidosis, free radicals, and the disturbance of the microcirculation seen in the early phase of recirculation. Glutamate is an excitatory neurotransmitter, which may turn neurotoxic when the energy supply is limited. Tissue acidosis down to pH 6.0 develops regularly in cerebral ischemia and disturbs a variety of neuronal functions, causing glial swelling and neuronal death. Free radicals attack brain lipids, the cell membrane and myelin in particular, and are produced during reperfusion. Disturbance of the microcirculation aggravates ischemic damage. Suggested therapeutic approaches include glutamate antagonists, normalization of tissue acidosis, and use of new diuretics to reduce glial swelling, protection of the brain by free radical scavengers such as 21-aminosteroids, tocopherol, allopurinol or superoxide dismutase, and hypothermia. Ways of ensuring fast reperfusion, including hypervolemic hemodilution and blood pressure stabilization, are suggested for resuscitation or early stroke. All data available indicate that the combination of several successful therapeutic principles will significantly improve outcome.
Institut für Neurochirurgische Pathophysiologie der Johannes Gutenberg-Universität Mainz.
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Kempski
D000818:Animals; D001925:Brain Damage, Chronic / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D015427:Reperfusion Injury / Q000503:physiopathology*
Neuroprotektion. Modelle und Grundprinzipien.