The mechanism of cerebral hypoxic‐ischemic damage

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Abstract
The four most prominent hypotheses on the cellular processes leading to hypoxic‐ischemic neuronal damage or death are (1) the lactacidosis hypothesis, (2) the calcium overload hypothesis, (3) the excitotoxic hypothesis, and (4) the oxygen‐free radical hypothesis. The authors comment on the evidence in favor of and against each in an attempt to select the one hypothesis that best explains the mechanism of cerebral hypoxic‐ischemic damage while withstanding the scrutiny of scientific testing. A major part of this inquiry is derived from in vitro studies that are suited to mechanistic exploration. They conclude that the calcium overload hypothesis is the best qualified in this respect. It is important to note, however, that some of the other hypothetical mechanisms may play a secondary role in exacerbating neuronal damage by accelerating calcium influx and overload.