title: Posttraumatic administration of a sub-anesthetic dose of ketamine exerts neuroprotection via attenuating inflammation and autophagy.
abstract: As a complex disease, traumatic brain injury (TBI) can result in long-term psychiatric changes and sensorimotor and cognitive impairments. The TBI-induced loss of memory and long-term cognitive dysfunction are related to mechanistic factors including an increased inflammatory response, autophagy, edema, and ischemia. Many published studies have offered evidence for the neuroprotective effects and anti-inflammatory properties of ketamine for TBI patients. Nonetheless, there is a limited understanding of the accurate mechanism that underlies the potential neuroprotective effects of ketamine. Herein, it can be shown that posttraumatic administration of ketamine at a sub-anesthetic dose (10mg/kg ketamine, every 24h up to 7days) can prevent the TBI-induced production of IL-6 and TNF-α, attenuate deficits of dendrites and spines and exert beneficial effects on memory and behavior. Moreover, studies show that ketamine may activate the mTOR signaling pathway by p-mTOR induction to down-regulate the expression of crucial autophagic proteins such as LC3 and Beclin-1. According to these findings, ameliorating secondary brain injury and anti-inflammatory properties is closely related to the neuroprotection of ketamine, which supports the use of ketamine as a potential therapy for patients with TBI to alleviate functional deficits.
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China; Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: C-Q
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: W-C
authors.initials: WC
authors.lastname: Han
authors.affiliation: Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Sun
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: R
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: K
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Zheng
authors.affiliation: College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: linchuanliao@scu.edu.cn.
authors.forename: L-C
authors.initials: LC
authors.lastname: Liao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000523:psychology; D003712:Dendrites / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D000255:Adenosine Triphosphate; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: autophagy; ketamine; mTOR; traumatic brain injury