Rolipram, a
phosphodiesterase-4 inhibitor, can activate the cyclic
adenosine monophosphate (cAMP)/cAMP-responsive
element binding protein (CREB) pathway to facilitate functional recovery following
ischemic stroke. However, to date, the effects of
rolipram on angiogenesis and
cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of
rolipram on the angiogenesis and neuronal apoptosis following brain
cerebral ischemia. Rat models of
ischemic stroke were established following transient
middle cerebral artery occlusion and
rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium
chloride staining, immunostaining and
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of
rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)
CREB protein level in the ischemic hemisphere. The
rolipram treatment group exhibited a marked reduction in
infarct size and modified neurological severity score compared with the vehicle group, and
rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-
CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the
rolipram group compared with the vehicle group. These findings suggest that
rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway.