title: 17AAG improves histological and functional outcomes in a rat CCI model through autophagy activation and apoptosis attenuation.
abstract: Traumatic brain injury (TBI) is caused by both primary and secondary injury mechanisms, all of which cause neuronal cell death and functional deficits. Both apoptosis and autophagy participated in neuronal cell death and functional loss induced following TBI. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, present neuroprotection actions in multiple neurological disorders, but whether 17-AAG is capable of modulating neuronal autophagy has never been addressed. The present study was designed to determine the hypothesis that17-AAG treatment could confer neuroprotection in a rat model of TBI. We also used an autophagy inhibitor 3-methyladenine (3-MA) as well as an autophagy inducer rapamycin (RAPA) to test its underlining mechanisms. Our results showed that post-TBI administration of 17-AAG could attenuate brain edema, decrease neuronal death, as well as improve the recovery of motor function. Afterwards, in our model, 17-AAG treatment protected against TBI-induced apoptosis activation as well as enhanced neuronal autophagy. The present study provides novel clues in understanding the mechanisms of which 17-AAG exerts its neuroprotective activity on neurological disorders.
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Zefu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Sui
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China. Electronic address: mlx_182019@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D016227:Benzoquinones / Q000627:therapeutic use*; D001929:Brain Edema / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D047029:Lactams, Macrocyclic / Q000627:therapeutic use*; D009048:Motor Skills / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D018696:Neuroprotective Agents; C112765:tanespimycin; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus
keywords: 17-AAG; Apoptosis; Autophagy; Functional recovery; TBI