title: Therapeutic effect of SN50, an inhibitor of nuclear factor-κB, in treatment of TBI in mice.
abstract: NF-κB upregulation has been demonstrated in neurons and glial cells in response to experimental injury and neuropathological disorders, where it has been related to both neurodegenerative and neuroprotective activities. It has been generally recognized that NF-κB plays important roles in the regulation of apoptosis and inflammation as well as innate and adaptive immunity. However, the regulatory mechanism of NF-κB in apoptosis remained to be determined. The present study sought to first investigate the effect of a NF-κB inhibitor SN50, which inhibits NF-κB nuclear translocation, on cell death and behavioral deficits in our mice traumatic brain injury (TBI) models. Additionally, we tried to elucidate the possible mechanisms of the therapeutic effect of SN50 through NF-κB regulating apoptotic and inflammatory pathway in vivo. Encouragingly, the results showed that pretreatment with SN50 remarkably attenuated TBI-induced cell death (detected by PI labeling), cumulative loss of cells (detected by lesion volume), and motor and cognitive dysfunction (detected by motor test and Morris water maze). To analyze the mechanism of SN50 on cell apoptotic and inflammatory signaling pathway, we thus assessed expression levels of TNF-α, cathepsin B and caspase-3, Bid cleavage and cytochrome c release in SN50-pretreated groups compared with those in saline vehicle groups. The results imply that through NF-κB/TNF-α/cathepsin networks SN50 may contribute to TBI-induced extrinsic and intrinsic apoptosis, and inflammatory pathways, which partly determined the fate of injured cells in our TBI model.
authors.affiliation: Department of Forensic Medicine, Soochow University, 199 Ren'ai Road, Suzhou Dushuhu High Educational Town, Suzhou 215123, People's Republic of China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Sun
authors.forename: Ding-Kun
authors.initials: DK
authors.lastname: Dai
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Luo
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Bao
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Feng
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Qin
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Tao
mesh_terms: D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010455:Peptides / Q000627:therapeutic use*; D011419:Propidium; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D011419:Propidium; D045304:Cytochromes c; D053148:Caspase 3; D002401:Cathepsin B