An increased understanding of the pathophysiological consequences of stroke and, in particular, the notion of an ischaemic penumbra in acute cerebral infarction has led to the development of novel neuroprotective treatments. These act at different stages of the pathophysiological cascade that leads to ischaemic neuronal damage.A bewildering number of potentially neuroprotective treatments are currently in preclinical and clinical development. This article systematically reviews all the completed and ongoing randomised controlled trials evaluating the effect of the more recently developed neuroprotective agents on clinical outcomes in patients with acute stroke. These agents are focused on because more detailed quantitative meta-analyses are available for many of the earlier neuroprotective agents.A simple classification of all the current neuroprotective agents on the basis of common potential mechanisms of action is presented. The agents are classified into 8 major groups: modulators of excitatory amino acids, modulators of calcium influx, metabolic activators, antioedema agents, inhibitors of leucocyte adhesion, free radical scavengers, promoters of membrane repair and those with an unknown mechanism of action.The data emerging from clinical trials of currently available neuroprotective therapies have not provided clear evidence of the benefit of this type of treatment. Further large randomised trials involving patients with both ischaemic and haemorrhagic stroke are required before the routine use of neuroprotective therapy in clinical practice can be recommended.
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