Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action

(')-Epigallocatechin gallate (EGCG) is a potent antioxidant that is neuroprotective against ischemia-induced brain damage. However, the neuroprotective effects and possible mechanisms of action of EGCG after hypoxia-ischemia (HI) have not been investigated. Therefore, we used a modified "Levine" model of HI to determine the effects of EGCG. Wistar rats were treated with either 0.9% saline or 50 mg/kg EGCG daily for 1 day and 1 h before HI induction and for a further 2 days post-HI. At 26-days-old, both groups underwent permanent left common carotid artery occlusion and exposure to 8% oxygen/92% nitrogen atmosphere for 1 h. Histological assessment showed that EGCG significantly reduced infarct volume (38.0±16.4 mm3) in comparison to HI + saline (99.6±15.6 mm3). In addition, EGCG significantly reduced total (622.6±85.8 pmol L-[3H]citrulline/30 min/mg protein) and inducible nitric oxide synthase (iNOS) activity (143.2±77.3 pmol L-[3H]citrulline/30 min/mg protein) in comparison to HI+saline controls (996.6±113.6 and 329.7±59.6 pmol L-[3H]citrulline/30 min/mg protein for total NOS and iNOS activity, respectively).