Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling
is essential for the maintenance of normal neuronal function. Increased oxidative
stress that occurs with aging was shown to impair neurovascular coupling, which likely
contributes to a significant age-related decline in higher brain function, increasing
the risk for vascular cognitive impairment (VCI). Resveratrol is a polyphenolic compound
that exerts significant anti-aging protective effects in large vessels but its effects
on the cerebromicrovasculature remain poorly defined. The present study was undertaken
to investigate the capacity of resveratrol to improve neurovascular coupling in aging.
In aged (24 months old) C57BL/6 mice L-NAME sensitive, NO-mediated CBF responses to
whisker stimulation and to the endothelium-dependent dilator acethylcholine (ACh)
were impaired as compared to those in young (3 months old) mice. Treatment of aged
mice with resveratrol rescued neurovascular coupling and ACh-induced responses, which
was associated with down-regulation of cortical expression of NADPH oxidase and decreased
levels of biomarkers of oxidative/nitrative stress (3-nitrotyrosine, 8-isoprostanes).
Resveratrol also attenuated age-related increases in ROS production in cultured cerebromicrovascular
endothelial cells (DCF fluorescence, flow cytometry). In conclusion, treatment with
resveratrol rescues cortical neurovascular coupling responses to increased neuronal
activity in aged mice, likely by restoring cerebromicrovascular endothelial function
via down-regulation of NADPH-oxidase derived ROS production. Beneficial cerebromicrovascular
effects of resveratrol likely contribute to its protective effects on higher brain
function in aging.