[Tracking along the path toward ischemic neuronal death].
BACKGROUND
During episodes of ischemia/anoxia, the neurochemical and environmental changes considered toxic for nervous tissue lie behind the characteristic abrupt massive cell depolarization (MCD). A strong resemblance with other pathologic events enable us to postulate that MCD is a different state of the tissue that includes among others the anoxic depolarization and Le o s spreading depression. MCD is an active event. Neurons enter and leave MCD suddenly and synchronously, and contrary to current belief, their membrane integrity is preserved and ion gradients are only reduced. Biophysical membrane properties are not compatible with some postulates based on endotoxines. There is a direct relation between MCD susceptibility of the different neuron types/nuclei and their vulnerability to ischemia/anoxia. Two different substates can be distinguished in the associated interstitial potentials that are likely related to neuronal and glial dysfunction, respectively. The different modes and timings of anoxic neuronal death depend on the duration of MCD, the functional integrity of the glial network, and the history of previous insults.


CONCLUSIONS
MCD is a cellular state of risk bridging life and death. Neurons die if they cannot exit, but may recover if they do promptly, although still have to face subtle changes as well initiated during MCD that will eventually lead them to a delayed death. Avoiding MCD is escaping death. From a clinical point of view, the relevant point is that manipulating MCD entails the simultaneous control of all toxic neurochemical concomitants. Reinforcing vulnerable neurons to avoid their falling into MCD is possible
Herreras
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O
Servicio de Neurobiología. Hospital Ramón y Cajal. Madrid. España. oscar.herreras@hrc.es
Largo
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D001923:Brain Chemistry; D016923:Cell Death / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000502:physiology*