Pathophysiology of cerebral ischaemia.

This article reviews the most currently used experimental models of cerebra l ischaemia. Mechanisms involved in ischaemic neuronal death are considered at the tissue, cellular and molecular levels. The various steps of the exc itotoxic cascade induced by anoxic depolarization in conditions of energy f ailure are analyzed, from excessive glutamate release to intracellular calc ium accumulation, massive calcium-dependent enzyme activation, and the form ation of oxygen radicals. Apoptotic neuronal death is also discussed, which leads one to distinguish between genes whose expression is beneficial or d eleterious in ischaemic conditions. Finally, the putative causes of contrad ictory results obtained from pharmacological studies in animals and humans are discussed. (C) 1999 Elsevier, Paris.