title: Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats.
abstract: Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology. Blood-spinal cord barrier (BSCB) permeability, tissue edema formation, microglial activation, neuronal cell death and myelin loss were determined in rats subjected to spinal cord contusion. The results showed that tamoxifen, administered at 30 min post-injury, significantly decreased interleukin-1beta (IL-1beta) production induced by microglial activation, alleviated the amount of Evans blue leakage and edema formation. In addition, tamoxifen treatment clearly reduced the number of apoptotic neurons post-SCI. The myelin loss and the increase in production of myelin-associated axonal growth inhibitors were also found to be significantly attenuated at day 3 post-injury. Furthermore, rats treated with tamoxifen scored much higher on the locomotor rating scale after SCI than did vehicle-treated rats, suggesting improved functional outcome after SCI. Together, these results demonstrate that tamoxifen provides neuroprotective effects for treatment of SCI-related pathology and disability, and is therefore a potential neuroprotectant for human spinal cord injury therapy.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dai-Shi
authors.initials: DS
authors.lastname: Tian
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Qu
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Yu
authors.forename: Zhou-Ping
authors.initials: ZP
authors.lastname: Tang
authors.forename: Deng-Ji
authors.initials: DJ
authors.lastname: Pan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004487:Edema / Q000188:drug therapy / Q000209:etiology; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D000070798:Nogo Proteins; D010446:Peptide Fragments / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D004965:Estrogen Antagonists; D007211:Indoles; D053583:Interleukin-1beta; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; D010446:Peptide Fragments; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat; D013629:Tamoxifen; C052994:interleukin-1beta (163-171); C018588:Luxol Fast Blue MBS; D010751:Phosphopyruvate Hydratase