CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, 
although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) 
has shown that global recovery is similar in CDP-choline and placebo groups, 
CDP-choline was shown to be more beneficial in some patients, such as those with 
moderate stroke severity and not treated with t-PA. Several mechanisms have been 
proposed to explain the beneficial actions of CDP-choline. We have now studied 
the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of 
CDP-choline. Fischer rats and Sirt1⁻/⁻ mice were subjected to permanent focal 
ischemia. CDP-choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), 
and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered 
intraperitoneally. Brains were removed 24 and 48 h after ischemia for western 
blot analysis and infarct volume determination. Treatment with CDP-choline 
increased SIRT1 protein levels in brain concomitantly to neuroprotection. 
Treatment with sirtinol blocked the reduction in infarct volume caused by 
CDP-choline, whereas resveratrol elicited a strong synergistic neuroprotective 
effect with CDP-choline. CDP-choline failed to reduce infarct volume in Sirt1⁻/⁻ 
mice. Our present results demonstrate a robust effect of CDP-choline like SIRT1 
activator by up-regulating its expression. Our findings suggest that therapeutic 
strategies to activate SIRT1 may be useful in the treatment of stroke. Sirtuin 1 
(SIRT1) is implicated in a wide range of cellular functions. Regarding stroke, 
there is no direct evidence. We have demonstrated that citicoline increases 
SIRT1 protein levels in brain concomitantly to neuroprotection. Citicoline fails 
to reduce infarct volume in Sirt1⁻/⁻ mice. Our findings suggest that therapeutic 
strategies acting on SIRT1 may be useful in the treatment of stroke.