Ischemia-mediated neuronal injury.
Resuscitation of the brain after a period of global ischemia is limited by two classes of post-ischemic pathologies: hemodynamic disturbances which prevent the adequate re-oxygenation of the ischemic brain, and metabolic disturbances which may lead to delayed neuronal death in so-called selectively vulnerable brain regions. The hemodynamic disturbances can be classified into the no-reflow phenomenon and the post-ischemic hypoperfusion syndrome. The no-reflow phenomenon results from a combination of increased blood viscosity and perivascular edema; the severity increases with the duration of ischemia, and the treatment is by combining arterial hypertension with dehydration and anticoagulation. The post-ischemic hypoperfusion syndrome is independent of the duration of ischemia, it develops after a delay and is due to an impairment of the metabolic/hemodynamic coupling mechanisms; there is no specific treatment at the present. The most important metabolic disturbance leading to delayed neuronal death is prolonged inhibition of protein synthesis. The injury is manifested already after 5 min ischemia but it progresses little if ischemia is prolonged to 1 h. Inhibition occurs at the translation level due to selective inhibition of polypeptide chain initiation. After brief periods of ischemia, the disturbance can be reversed by various anesthetics and hypothermia but there is no treatment if ischemia is prolonged. Exitotoxity, free radical-mediated reactions, disturbances of polyamine metabolism, acidosis and selective disturbances of gene expression may also be involved but are probably of lesser importance.
Hossmann
K A
KA
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia; D016923:Cell Death; D002560:Cerebrovascular Circulation / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000473:pathology*; D015427:Reperfusion Injury; D012151:Resuscitation; D012270:Ribosomes / Q000378:metabolism