title: Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: autophagy and the PI3K/AKT pathways as a potential mechanism.
abstract: Tetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI.
  
  
  
  Behavioral studies were performed by recording and analyzing beam-walking scores. The role of tetrahydrocurcumin on neurons death was assessed via Nissl staining. We then performed Western blot analyses, terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling assays and immunofluorescence staining to evaluate autophagy and apoptosis. Phospho-protein kinase B (p-AKT) was also assessed via Western blotting.
  
  
  
  Our data indicated that administration of tetrahydrocurcumin alleviated brain edema, attenuated TBI-induced neuron cell death, decreased the degree of apoptosis and improved neurobehavioral function, which were accompanied by enhanced autophagy and phospho-AKT after TBI. Moreover, the autophagy inhibitor 3-methyladenine and the PI3K kinase inhibitor LY294002 partially reversed the neuroprotection of tetrahydrocurcumin after TBI.
  
  
  
  This study indicates that tetrahydrocurcumin protects neurons from TBI-induced apoptotic neuronal death, which may be through modulation autophagy and PI3K/AKT pathways. Thus, tetrahydrocurcumin may be an attractive therapeutic agent for TBI.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njLijiepro@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; C096277:tetrahydrocurcumin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: Apoptosis; Autophagy; PI3K/AKT signaling pathway; Tetrahydrocurcumin; Traumatic brain injury