We have previously shown that
NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)
pyrimidine hydrochloride] reduces the size of
cerebral infarction measured by
2,3,5-triphenyltetrazolium chloride staining at 48 h after permanent
middle cerebral artery occlusion (MCAO) in rats. To determine whether
NS-7 improves the pathological and behavioral changes at the chronic stage of MCAO, the effect of this compound on the
cerebral infarction as well as the neurological and
cognitive impairments was investigated 7 days after MCAO. Single or five daily
injections of
NS-7 (0.125-0.5 mg/kg, i.v.) significantly reduced the
infarct volume and improved the neuronal dysfunction including the hind leg
paralysis, walking disability and motor
incoordination, and the deficit of passive avoidance task, although the neuroprotective efficacy was not different among these dosing regimens. On the other hand, the effects of single versus repeated
injections of
NS-7 at 0.1 or 0.2 mg/kg on the neurological symptoms were compared at 4 weeks after MCAO. At a lower dose, repeated but not single injection of
NS-7 significantly improved the neurological symptoms, although the single injection was effective at a higher dose. From these findings, it is suggested that
NS-7 reverses the behavioral and
cognitive dysfunction observed at the chronic stage of
cerebral ischemia by suppressing the
cerebral infarction.