Neuroprotection aims to prevent salvageable neurons from dying. Despite showing 
efficacy in experimental stroke studies, the concept of neuroprotection has 
failed in clinical trials. Reasons for the translational difficulties include a 
lack of methodological agreement between preclinical and clinical studies and 
the heterogeneity of stroke in humans compared to homogeneous strokes in animal 
models. Even when the international recommendations for preclinical stroke 
research, the Stroke Academic Industry Roundtable (STAIR) criteria, were 
followed, we have still seen limited success in the clinic, examples being 
NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR 
criteria. However, there are a number of neuroprotective treatments under 
investigation in clinical trials such as hypothermia and ebselen. Moreover, 
promising neuroprotective treatments based on a deeper understanding of the 
complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases 
and PSD-95 are currently evaluated in preclinical studies. Further concepts to 
improve translation include the investigation of neuroprotectants in multicenter 
preclinical Phase III-type studies, improved animal models, and close alignment 
between clinical trial and preclinical methodologies. Future successful 
translation will require both new concepts for preclinical testing and 
innovative approaches based on mechanistic insights into the ischemic cascade.