Molecular mechanisms for ischemic brain damage and aspects on protection.

Multiple factors are responsible for the development of irreversible cell damage in the ischemic brain. Different molecular mechanisms may operate alone or may influence each other to create a vicious circle leading to a point of no-return. Tissue energy failure, disruption of ionic homeostasis, and severe tissue lactic acidosis can be regarded as major basic mechanisms that provoke a sequence of events finally leading to degradation and death of brain cells. Accumulation of calcium, liberation of free fatty acids, and pathologic free radical reactions during the postischemic phase may have additional pathogenetic significance. Possibilities to protect the ischemic brain are discussed with respect to the different pathogenetic mechanisms. Primarily, these include measures taken to decrease the cerebral energy demands and to prevent the development of severe tissue lactic acidosis.