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.
Toth P, Tarantini S, Tucsek Z, Ashpole NM, Sosnowska D, Gautam T, Ballabh P, Koller A, Sonntag WE, Csiszar A, Ungvari ZI. Resveratrol treatment rescues neurovascular coupling in aged mice:role of improved cerebromicrovascular endothelial function and down-regulation of NADPH oxidas. Am J Physiol Heart Circ Physiol. 2013 December University of Oklahoma Health Sciences Center.