Disturbances of calcium homeostasis in ischaemic stroke - Therapeutic implications

In Western societies, stroke represents the third largest cause of death an d the main cause of disability. With an expected increase of stroke inciden ce in the near future, much research is being devoted to the development of an effective treatment. At present, however, no such treatment is availabl e, although thrombolysis may be beneficial in a small percentage of patient s with ischaemic stroke. The use of neuroprotective agents that protect neurons against the effects of ischaemia is appealing. Some neuroprotective drugs are believed to exert their effects by influencing calcium homeostasis in potentially viable bra in cells in the ischaemic penumbra, the area surrounding the core of the in farct. A massive calcium ion (Ca++) influx into these cells plays an import ant role in the final common pathway of cell death. Ca++ can enter cells by voltage-sensitive calcium channels or by agonist-operated calcium channels . Calcium antagonists acting on several subtypes of these channels are capa ble of decreasing Ca++ influx into ischaemic brain cells. In animal studies, many calcium antagonists reduce infarct size or increase cerebral blood flow. However, clinical trials with calcium antagonists hav e been disappointing and at present an effective neuroprotective agent has not been identified. Recently, concerns have arisen about the adverse effec ts of calcium antagonists acting on voltage-sensitive calcium channels.