Neuroprotection in acute ischaemic stroke. Current status and future potential

Acute ischaemic strokes can potentially be treated by 2 different mechanisms: lysing the thrombus to enhance brain perfusion or salvaging brain tissue directly. Neuroprotective agents are designed to try to salvage brain tissue. They work either during acute ischaemia or during reperfusion, when additional brain injury may occur. Despite the completion of a number of clinical trials investigating neuroprotective agents that have various mechanisms of action, as yet no effective agent has been identified. Some drugs, such as N-methyl-D-aspartate (NMDA) receptor antagonists and anti-leucocyte adhesion agents, have been limited by adverse effects and drug reactions. However, the development of other agents in these classes that have better risk to benefit ratios may lead to an effective neuroprotective drug. Other drugs, including citicoline, clomethiazole and nalmefene, have more efficacy in certain patient subgroups than in the stroke population as a whole. Therefore, targeting these agents toward the groups in which they are most likely to work, such as patients with a certain size of stroke, may uncover efficacy. Encouragingly, a number of drugs that are in the early stages of development, such as YM 872, Bay X 3702 and BMS 204352, appear to offer new hope for neuroprotection.