The Potential Role Of Astaxanthin In Early Brain Injury After Experimental Subarachnoid Hemorrhage

Background and Purpose：Accumulating studies indicated early braininjury (EBI) is the primary cause of mortality in SAH patients. Therefore,treatment of EBI has been considered as a main goal in the management ofpatients with SAH. Although the mechanism of EBI is complicated,increasing studies indicate that oxidative damage plays a critical role in EBIpathogenesis and may represent a novel target for treatment of SAH.Astaxanthin (ATX) is a more powerful antioxidan. In previous studies, ATXhas been used as an antioxidant therapeutic agent in models of cardiovasculardisease including myocardial ischemia and reperfusion. However, there is nostudy to investigate the effects of ATX on experimental SAH. Based on thesedata, we tried to use various models, species and administration method toexplore the potential effects and mechanisms of ATX in EBI following SAHin the present study. To further demonstrate the possible benefits of ATX andto investigate the clinical utility of ATX, delayed dosing via oraladministration were used. The current study will establish a rationale forfuture therapies in SAH.Methods: The prechiasmatic cistern rat SAH model andone-hemorrhage rabbit SAH model were performed. Intracerebroventricularinjection and oral administration were used in this experiment. Body weightand clinical evaluation were recorded to observe the therapies on overallcondition after SAH. The brain water content was perfomed to reflect theeffects of ATX on brain edema. The Evans blue extravastion was performed toevaluate the effects of ATX on blood-brain barrier permeability. Western-blotwas conducted to detect the expreesion of caspase-3in the cerebral cortexafter SAH. Immunohistochemistry was performed to observe the cellularlocalization and distribution of caspase-3and neurodegeneration in cerebralcortex. Spectrophotometric method were used to evaluate the benefical effectsof ATX on oxidative stress after SAH. Results: It was observed that treatment with ATX could significantlyreduce brain edema, BBB disruption and neurodegenerationr after SAH in theprechiasmatic SAH model. Delayed treatment with ATX at3hr after SAHcould also reduce EBI, including brain edema, BBB disruption andneurodegenerationr. These benefical effects were associated with its powerfulantioxidant property. In the one-hemorrhage rabbit SAH model, delayedtreatment with ATX also significantly attenuated EBI after SAH andprevented oxidative damage in the cerebral cortex.Conclusions: Post-SAH ATX administration by intracerebroventricularinjection could alleviate EBI after SAH. Delayed treatment with ATXadministration by oral administration also showed significant neuroprotectionin EBI after SAH. And These benefical effects were associated with itspowerful antioxidant property. This present research was the first one todemonstrate that ATX administration by intracerebroventricular injection andoral administration could ameliorate EBI in experimental SAH models. Thebeneficial effects of ATX might be associated with suppressing oxidativestress damage, and up-regulating the levels of endogenous antioxidants..