Calcium transients in brain ischemia: role in neuronal injury

Abstract

The involvement of calcium ions in mechanisms of ischemic brain injury has been suggested for several years. Our understanding of the role of intracellular Ca2+ as a trigger of acute neurotoxicity and in the induction of long lasting processes leading to necrotic and/or apoptotic postischemic delayed neuronal death or of compensatory, neuroprotective mechanisms has increased considerably. Still many questions concerning the generation of Ca2+ signal such as the nature of the main routes of ischemic Ca2+ influx to neurones, involvement of intracellular Ca2+ stores and Ca2+ buffers, spatial and temporal relations between ischemia-induced increases in intracellular Ca2+ concentration and neurotoxicity remain open. Some conclusions from experiments in cultured neurones concerning glutamate-evoked destabilization of Ca2+ homeostasis and neurotoxicity may be not relevant to in vivo ischemic conditions. This review, apart from emphasising generally proposed mechanisms of Ca2+ transients and toxicity in ischemic neurones, will discuss some of these controversial issues.