title: Astaxanthin alleviates cerebral edema by modulating NKCC1 and AQP4 expression after traumatic brain injury in mice.
abstract: Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI).
  
  
  
  Our results showed that, following CCI, treatment with astaxanthin compared to vehicle ameliorated neurologic dysfunctions after day 3 and alleviated cerebral edema and Evans blue extravasation at 24 h (p < 0.05). Astaxanthin treatment decreased AQP4 and NKCC1 mRNA levels in a dose-dependent manner at 24 h. AQP4 and NKCC1 protein expressions in the peri-contusional cortex were significantly reduced by astaxanthin at 24 h (p < 0.05). Furthermore, we also found that bumetanide (BU), an inhibitor of NKCC1, inhibited trauma-induced AQP4 upregulation (p < 0.05).
  
  
  
  Our data suggest that astaxanthin reduces TBI-related injury in brain tissue by ameliorating AQP4/NKCC1-mediated cerebral edema and that NKCC1 contributes to the upregulation of AQP4 after TBI.
authors: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors: Mingkun
authors: M
authors: Zhang
authors: Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266005, China.
authors: Zhenwen
authors: Z
authors: Cui
authors: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors: Hua
authors: H
authors: Cui
authors: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
authors: Yang
authors: Y
authors: Cao
authors: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. drchunlongzhong@126.com.
authors: Chunlong
authors: 0000-0002-0605-7273
authors: C
authors: Zhong
authors: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. wangyong68@163.com.
authors: Yong
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002034:Bumetanide / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C578878:Slc12a2 protein, mouse; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D024341:Xanthophylls; D002034:Bumetanide; C005948:astaxanthine
keywords: Aquaporin-4; Astaxanthin; Cerebral edema; Na+–K+–2Cl− co-transporter-1; Traumatic brain injury