• Mingkun Zhang, Zhenwen Cui, Hua Cui, Yong Wang, and Chunlong Zhong.
• Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
• Bmc Neurosci. 2017 May 10; 18 (1): 42.

BackgroundAstaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na+-K+-2Cl- co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice. This paper explored the molecular mechanism of ATX-mediated inhibition of NKCC1 utilizing an in vitro astrocyte stretch injury model.ResultsStretch injury in cultured astrocytes lowered cell viability time-dependently, which was substantially reducing by pretreating with ATX (50 μmol/L). Stretch injury increased Bax level and cleaved caspase-3 activity, and decreased Bcl-2 level and pro-caspase 3 activity, resulting in the apoptosis of astrocytes. Additionally, stretch injury substantially raised the gene and protein expressions of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and prompted the expression and nuclear translocation of NF-κB. Pretreatment with ATX remarkably prevented the trauma-induced initiation of NF-κB, expressions of pro-inflammatory cytokines, and cell apoptosis. Moreover, stretch injury markedly elevated the gene and protein expression of NKCC1, which was partly blocked by co-treatment with ATX (50 µmol/L) or an NF-κB inhibitor (PDTC, 10 µmol/L). Cleaved caspase-3 activity was partially reduced by PDTC (10 µmol/L) or an NKCC1 inhibitor (bumetanide, 50 µmol/L).ConclusionsATX attenuates apoptosis after stretch injury in cultured astrocytes by inhibiting NKCC1 expression, and it acts by reducing the expression of NF-κB-mediated pro-inflammatory factors.

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