Our recent study demonstrated that
nefiracetam, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)
acetamide, prevented impairment of the
cyclic AMP (cAMP)/cAMP-responsive
element binding (
CREB) protein signaling pathway in sustained
cerebral ischemia. The purpose of the present study was to determine whether
nefiracetam has an effect on the expression of
brain-derived neurotrophic factor (
BDNF) and
synapsin I mRNAs that are believed to be produced via CREB, and the alteration in their
protein contents in the hippocampus after
cerebral ischemia. Sustained
cerebral ischemia was induced by injection of 700
microspheres into the right hemisphere of each rat. The rats were treated once daily with 10 mg/kg
nefiracetam, p.o., from 15 h after the operation. Treatment with
nefiracetam reduced the prolongation of the escape latency in the water maze test on days 7-9 after
microsphere embolism-induced sustained
cerebral ischemia, suggesting an improvement in the spatial learning function.
Microsphere-embolized rats on day 5 showed decreases in
BDNF and
synapsin I mRNA levels and their
protein contents in the ipsilateral hippocampus. Treatment with
nefiracetam partially attenuated the decreases. These results suggest that enhancement of
BDNF and
synapsin I expression by
nefiracetam treatment may be, at least in part, due to the improvement in the CREB binding activity, contributing to the prevention of learning and memory dysfunction after sustained
cerebral ischemia.