Preventive and curative effects of grape seed powder on stroke using in vitro and in vivo models of cerebral ischemia/reperfusion.

Stroke is a worldwide concern. Many studies pointed out relevant preventive effect of grape seed powder (GSP) against deleterious brain ischemia/reperfusion (I/R) injury, but curative effect has been scarcely approached. The present work aimed at studying the preventive and curative effect of GSP against stroke using in-vitro and in-vivo models. Primary neuron-astrocyte cocultures were used to evaluate in-vitro GSP protective and curative effect on oxygen-glucose-deprivation (OGD). A murine I/R model, in which GSP was administered as delayed post stroke drug, to evaluate its potential clinically translatable therapy was used and behavioral tests were conducted after 15 days. Ultra-structure of hippocampus dentate gyrus using Transmission Electron Microscopy (TEM) was also undertaken. GSP prevented OGD-induced toxicity and cell death in a dose dependent manner and was neuroprotective as assessed by sustained cell viability (70 % ±1 for OGD + GSP and 37 % ±2 for OGD) and modulated cytokines and brain derived neurotrophic factor (BDNF) expression. GSP also promoted behavioral outcomes by increasing step-down inhibitory time from 17s±4 to 50s±11 and rat overall activities by improving scores in open field test to near control level. Furthermore, GSP protected hippocampus dentate gyrus area from I/R-induced drastic alterations as assessed by reduced autophagic vacuoles.