1 nmol. Our previous report showed that 10 nmol of serofendic acid with intracerebroventricular treatment was required Baf-A1 clinical trial to exhibit the protective effect on ischemic neuronal damage (Nakamura et al., 2008). Thus, we predicted that serofendic acid may fail to protect

the brain from ischemia-reperfusion injury when administered intravenously. Contrary to our expectations, intravenous administration of serofendic acid exerted protective effects on cerebral ischemia-reperfusion injury without affecting rCBF and physiological parameters. While serofendic acid has a relatively low ability to penetrate the blood brain barrier (BBB), it can be detected in the brain after intravenous administration (Terauchi et al., 2007). We assume that its low concentration in the brain is able to exert a protective effect since a low dose (10–30 nmol) of intracerebroventricularly administered serofendic acid was effective on cerebral ischemia-reperfusion injury (Nakamura et al., 2008). Thus, the small amount of serofendic acid that penetrates into the brain tissue may be sufficient to protect cells from ischemia-reperfusion injury. Since cerebral ischemia-reperfusion injury leads to the breakdown of check details BBB, molecules that cannot infiltrate the BBB in normal conditions

may be able to do so more in case of cerebral ischemia-reperfusion injury (Haile et al., 2010 and Michalski et al., 2010). It is possible that serofendic acid may pass through the injured BBB more easily IMP dehydrogenase than under normal conditions. Further studies are needed to determine whether BBB disruption is required for a sufficient amount of serofendic acid to pass through. In the present

study, three administrations of serofendic acid exerted protective effects on cerebral ischemia-reperfusion injury, whereas single administration did not protect from ischemia-reperfusion injury. In our previous study, serofendic acid exhibited a high clearance value when administered intravenously (T1/2: 0.65 h) ( Terauchi et al., 2007). Thus, the protective effects from three administrations of serofendic acid are not because of the total dose (30 mg/kg) but because of persistent blood concentrations. We showed that protective effect of serofendic acid administrated intravenously requires pretreatment before ischemia, whereas serofendic acid intracerebroventricularly administered at 30 min after the onset of ischemia protected brain from ischemia-reperfusion injury ( Nakamura et al., 2008). This difference may have occurred owing to the poor ability of serofendic acid to penetrate BBB or be retained in the brain tissue. Regulation of pharmacokinetics of serofendic acid may enable serofendic acid administered intravenously after the onset of ischemia to exert protective effect on ischemia-reperfusion injury.