title: 17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal autophagic death induced by transient global cerebral ischemia.
abstract: Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Jianxiong
authors: J
authors: Li
authors: Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China.
authors: Fei
authors: F
authors: Yang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Jia
authors: J
authors: Guo
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Rongrong
authors: R
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Xiangfeng
authors: X
authors: Xing
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: xinyueqin24k@163.com.
authors: Xinyue
authors: X
authors: Qin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D016227:Benzoquinones / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016227:Benzoquinones; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018696:Neuroprotective Agents; D018697:Nootropic Agents; C112765:tanespimycin
keywords: 17-AAG; Autophagy; Functional recovery; GCI; Hsp70; Inflammatory response