Neuroprotective strategy in an experimental newborn rat model of brain ischemia and hypoxia: effects of Resveratrol and hypothermia.

Introduction: Cerebral hypoxia and ischemia are the major causes of perinatal mortality resulting in central nervous system injury. Hypoxia and ischemia produce massive brain damage and one of the most important mechanisms in the lesion pattern is oxidative stress.

Aims: The objectives of this study are to assess the effects of resveratrol pretreatment in a cerebral hypoxic-ischemic (HI) newborn rat model as well as the influence that hypothermia has on redox parameters in this experimental model and the effects of the combined therapy from the oxidative stress perspective.

Material And Method: The experiment was performed on eighty newborn Wistar rats of both genders, weighing about 10 grams, placed into eight groups: control, treated with resveratrol (RES), RES+HI insult, RES+hypothermia, subjected to hypothermia only, HI insult+normothermia, HI insult+hypothermia. Resveratrol was administrated 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 order to test the effect of combined therapy of resveratrol with hypothermia, several animals were exposed after HI injury to whole body moderate hypothermia (with 4°C) for 3h. After recovery the malondialdehyde level and the activities of superoxide dismutase and glutathione peroxidase were determined in the brain tissue of the newborn rats.

Results: MDA levels were increased in the groups receiving resveratrol pretreatment. In the group subjected to simple hypothermia MDA levels were also increased. In the group subjected to HI insult and then to hypothermia, MDA levels were significantly lower. MDA levels were lower also in the group where RES was associated with hypothermia in HI insult context. GPx levels were decreased in groups pretreated with RES and subjected to HI, hypothermia, the same effect in case of hypothermia alone. Only in the group treated with RES was the GPx level higher than in controls. SOD levels were high in the RES pretreated group, but decreased in HI insult. In the group subjected to hypothermia after HI, SOD was significantly higher.

Conclusion: The results of this study prove that hypothermia offers better neuroprotection in ischemic brain injuries than resveratrol. The combined therapy influenced the oxidative stress parameters. Hypothermia is a stress factor, but when applied in post-lesion condition, offers protection for the brain.