Oral administration of grape polyphenol extract ameliorates cerebral ischemia/reperfusion-induced neuronal damage and behavioral deficits in gerbils: comparison of pre- and post-ischemic administration

Oxidative stress has been regarded as an important underlying cause for the delayed neuronal death (DND) after cerebral ischemia. In this study, the effects of short-term oral administration of grape polyphenol extract (GPE) on ischemia/reperfusion (I/R) injury in a gerbil global ischemia model were determined. Ischemia was induced by occlusion of the common carotid arteries for 5 min. GPE (30 mg/ml)-containing formula or formula without GPE was administered daily via gavage for 4 days prior to and/or for 4 days after I/R. I/R resulted in hyperlocomotion, extensive DND, oxidative and fragmented DNA damage, and an increase in reactive astrocytes and microglial cells in the hippocampal CA1 region. GPE administration for 4 days prior to I/R and for 4 days after I/R attenuated DND, DNA damage and glial cell activation. However, neuroprotection was more pronounced when GPE was administered for 4 days after I/R than when administered for 4 days prior to I/R. GPE administration after I/R attenuated I/R-induced hyperlocomotion. These findings indicate that oral GPE intake may confer protection against I/R injury and emphasize that early intervention may be an effective therapeutic measure for ameliorating brain injury in stroke.