Cerebral ischemia revisited: new insights as revealed using in vitro brain slice preparations

The elucidation of the pathophysiological mechanisms of cerebral ischemia/hypoxia dictates the use of experimental models which mimic this disabling brain condition. In vivo experimental models have been available for many decades and are responsible for the bulk of, though incomplete, knowledge we have about these mechanisms. Since study in isolation of each postulated mechanism is impossible in vivo, the need for an in vitro experimental model has intensified in recent years. Consequently, rat and guinea pig hippocampal slice preparations have emerged as the models of choice. This review attempts to highlight some of the results obtained using brain slices in the study of cerebral ischemia/hypoxia and compare them to those obtained in vivo. Both the biochemical and the physiological correlates of energy metabolism, ion homeostasis, neurotransmission and neuromodulation of this brain condition are reviewed. The agreements, and especially the disagreements, between the in vivo and in vitro findings are emphasized. Details are given of the possible roles of both lactic acid, Ca2+ and excitotoxins in the neuronal damage inflicted by cerebral ischemia/hypoxia. Recent attempts to protect brain slices against experimental cerebral ischemic/hypoxic damage are also reviewed here briefly.