Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

Laboratory investigation

Xiang-Sheng Zhang M.D. 1 , Xin Zhang M.D., Ph.D. 1 , 2 , Meng-Liang Zhou M.D., Ph.D. 2 , Xiao-Ming Zhou M.D. 1 , Ning Li M.D. 1 , Wei Li M.D. 2 , Zi-Xiang Cong M.D. 2 , Qing Sun M.D. 2 , Zong Zhuang M.D. 2 , Chun-Xi Wang M.D. 2 and Ji-Xin Shi M.D., Ph.D. 2
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  • 1 Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China; and
  • 2 Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China

Object

Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property.

Methods

Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation.

Results

It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH.

Conclusions

These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

Abbreviations used in this paper:ATX = astaxanthin; BBB = blood-brain barrier; DAB = 3,3′-diaminobenzidine; EB = Evans blue; EBI = early brain injury; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; GSH = glutathione; H2O2 = hydrogen peroxide; MDA = malondialdehyde; PBS = phosphate-buffered saline; SAH = subarachnoid hemorrhage; SOD = superoxide dismutase; TBS-T = Tris-buffered saline with Tween 20.

Contributor Notes

Address correspondence to: Xin Zhang, M.D., Ph.D., Department of Neurosurgery, Jinling Hospital, School of Medicine, Second Military Medical University, Shanghai, China. email: zhangxsp@163.com.

Please include this information when citing this paper: published online April 11, 2014; DOI: 10.3171/2014.2.JNS13730.

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