Astaxanthin Confers a Significant Attenuation of Hippocampal Neuronal Loss Induced by Severe Ischemia-Reperfusion Injury in Gerbils by Reducing Oxidative Stress

Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment.