Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury.
A previous study from our lab has shown that the polyphenol-rich pomegranate juice can protect the neonatal mouse brain against hypoxic-ischemic (H-I) injury when given to mothers in their drinking water. To test the hypothesis that this protection is due to the polyphenols in the juice, we studied the effects of the pomegranate polyphenol extract in the same neonatal H-I model. To further explore the role of a specific polyphenol in neonatal H-I we investigated the effects of resveratrol. The neuroprotective effects of resveratrol have been demonstrated in adult models of stroke, but had not previously been examined in neonates. We show that pomegranate polyphenols and resveratrol reduce caspase-3 activation following neonatal H-I. Resveratrol reduced caspase-3 activation when given before the injury but not when given 3 h after the injury. In addition to preventing caspase-3 activation, resveratrol also reduced calpain activation. Finally, we show that resveratrol can protect against tissue loss measured at 7 days after the injury. These and other recent findings suggest that polyphenols should be further investigated as a potential treatment to decrease brain injury due to neonatal H-I.
West
Tim
T
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Atzeva
Madeliene
M
Holtzman
David M
DM
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001720:Birth Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D029561:Lythraceae / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000975:Antioxidants; D061945:Caspase Inhibitors; D005419:Flavonoids; D018696:Neuroprotective Agents; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013267:Stilbenes; D002154:Calpain; D053148:Caspase 3; D000077185:Resveratrol