title: Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.
abstract: Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, Shijiazhuang Obstetrics and Gynecology Hospital, The Fourth Hospital of Shijiazhuang, Shijiazhuang 050011, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Rehabilitation, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Meng
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang 050017, China; Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, China. Electronic address: peiyuanlu@163.com.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002340:Carotid Artery Diseases; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007859:Learning Disabilities / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018697:Nootropic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D018021:Lithium Chloride
keywords: BDNF; Bax; Bcl-2; Learning; Lithium chloride; Memory; Repeated cerebral ischemia-reperfusion; p-CREB