The SAINT II Trial, a large randomized multicenter clinical trial of the 
putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in 
acute ischemic stroke. The further development of this agent was suspended. The 
implications of this outcome are considered from several perspectives, 
including: (1) the marginally positive antecedent trial, SAINT I, and the 
critical commentary stimulated by it, which called attention to its 
interpretively challenging primary outcome measure--a shift in the full-scale 
modified Rankin scale score--and to other statistical shortcomings; (2) the 
cogency of the STAIR recommendations, to which the development of NXY-059 
closely adhered; and (3) the inherent physiochemical shortcomings of NXY-059 as 
a neuroprotective agent--its polar, nonlipophilic nature, poor blood-brain 
barrier penetrability, nonphysiological oxidation potential, and low potency. 
Caution is urged, however, regarding the unwarranted adoption of a nihilistic 
view toward neuroprotection on the part of the stroke community in view of the 
abundant preclinical evidence demonstrating proof-of-principle of the 
feasibility of neuroprotection, as well as the multiplicity of biochemical and 
molecular neuroprotective targets. The author offers the personal example of a 
translational journey in which a promising neuroprotectant agent targeting 
multiple injury mechanisms, high-dose albumin therapy, has proceeded 
successfully from preclinical studies that established efficacy through a pilot 
clinical trial that demonstrated safety and offered strong suggestions of 
clinical efficacy, leading to a large multicenter clinical trial currently in 
progress.