title: Astaxanthin improves cognitive performance in mice following mild traumatic brain injury.
abstract: Traumatic brain injury (TBI) produces lasting neurological deficits that plague patients and physicians. To date, there is no effective method to combat the source of this problem. Here, we utilized a mild, closed head TBI model to determine the modulatory effects of a natural dietary compound, astaxanthin (AST). AST is centrally active following oral administration and is neuroprotective in experimental brain ischemia/stroke and subarachnoid hemorrhage (SAH) models. We examined the effects of oral AST on the long-term neurological functional recovery and histological outcomes following moderate TBI in a mice model.
  
  
  
  Male adult ICR mice were divided into 3 groups: (1) Sham+olive oil vehicle treated, (2) TBI+olive oil vehicle treated, and (3) TBI+AST. The olive oil vehicle or AST were administered via oral gavage at scheduled time points. Closed head brain injury was applied using M.A. Flierl weight-drop method. NSS, Rotarod, ORT, and Y-maze were performed to test the behavioral or neurological outcome. The brain sections from the mice were stained with H&E and cresyl-violet to test the injured lesion volume and neuronal loss. Western blot analysis was performed to investigate the mechanisms of neuronal cell survival and neurological function improvement.
  
  
  
  AST administration improved the sensorimotor performance on the Neurological Severity Score (NSS) and rotarod test and enhanced cognitive function recovery in the object recognition test (ORT) and Y-maze test. Moreover, AST treatment reduced the lesion size and neuronal loss in the cortex compared with the vehicle-treated TBI group. AST also restored the levels of brain-derived neurotropic factor (BDNF), growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP) in the cerebral cortex, which indicates the promotion of neuronal survival and plasticity.
  
  
  
  To the best of our knowledge, this is the first study to demonstrate the protective role and the underlining mechanism of AST in TBI. Based on these neuroprotective actions and considering its longstanding clinical use, AST should be considered for the clinical treatment of TBI.
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University, Jing Shi Road, Jinan, Shandong 250014, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Peng
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China. Electronic address: luning301@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: The Department of Orthopaedic Surgery, Chinese People's Liberation Army General Hospital (301 Hospital), 28 Fuxing Road, Wukesong, Beijing 100000, China. Electronic address: tangpeifu301@126.com.
authors.forename: Peifu
authors.initials: P
authors.lastname: Tang
mesh_terms: D000818:Animals; D001924:Brain Concussion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D021641:Recognition, Psychology / Q000187:drug effects; D045442:Rotarod Performance Test; D012720:Severity of Illness Index; D065852:Spatial Memory / Q000187:drug effects; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D018697:Nootropic Agents; D024341:Xanthophylls; C005948:astaxanthine
keywords: Astaxanthin; Growth-associated protein; NSS; Object recognition test; Rotarod test; Synaptic protein; Traumatic brain injury; Y-maze