The Combined Therapy with Resveratrol and Hypothermia Prevents Apoptosis in a Neonatal Rat Model of Global Hypoxic-Ischemic Encephalopathy

Abstract

Birth asphyxia and newborn prematurity are the two major causes of perinatal mortality resulting in central nervous system (CNS) injury by hypoxia and ischemia. Hypoxia and ischemia produce massive brain damage following a typical pattern which is defined by selective vulnerability of the brain regions.The main objective of this study was to test the possible protective effect of resveratrol and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. The changes in terms of histology and apoptosis were determined in brain so as to assess the local damages induced by hypoxic ishemia. The experiment was performed on 17 newborn Wistar rats that were given resveratrol in a dose of 20 mg/kg/day for seven days as premedication. At the end of this period the animals were exposed to hypobaric hypoxia (9% O+2 for 90 minutes) and ischemia (by clamping the right carotid artery). In global hypoxic-ischemic encephalopathy the resveratrol at a dose of 20 mg/kg/day as premedication offers neuroprotection by reducing the number of cells expressing apoptosis in CA1, CA2, CA3 and dentate gyrus of the hippocampus under the conditions of conjugation with post-injury hypothermia. In the cerebral cortex the resveratrol protective effects were not hypothermia dependent. No protective effect of resveratrol was observed in thalamus after global hypoxic-ischemic encephalopathy. The results of this study prove that resveratrol offers neuroprotection in hypobaric hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation of the protective therapy with post-injury hypothermia treatment