title: Pre-treatment with nimodipine and 7.5% hypertonic saline protects aged rats against postoperative cognitive dysfunction via inhibiting hippocampal neuronal apoptosis.
abstract: This study aimed to investigate the effects of pre-treatment with nimodipine and 7.5% hypertonic saline (HS) on postoperative cognitive dysfunction (POCD) in aged rats.
  
  
  
  Healthy Sprague-Dawley aged rats were randomly assigned into 4 groups: POCD group, nimodipine group, HS group, and nimodipine+HS group. Rats in POCD group received normal saline injection and then splenectomy 30min later under 1.8% isoflurane inhalation for 2h. In remaining groups, rats received injection of 1mg/kg nimodipine (i.p) and/or 4ml/kg 7.5% HS (i.v) and then splenectomy. Morris water maze test was performed before and after surgery. The hippocampus was harvested for the detection of neuronal apoptosis rate (AR), cytoplasmic calcium ([Ca2+]i), Bcl-2 and Bax mRNA expression and hippocampal neuronal ultrastructure.
  
  
  
  When compared with POCD group, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced dramatically, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly (P<0.05) in nimodipine group, NS group and nimodipine+HS group. In addition, the latency to escape, neuronal AR, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio reduced markedly, but the times of crossing the platform and Bcl-2 mRNA expression increased significantly in nimodipine+HS group as compared to nimodipine group and NS group (P<0.05). Hippocampal neuronal ultrastructure damage was observed in all 4 groups, but it was the mildest in nimodipine+HS group.
  
  
  
  Pre-treatment with both nimodipine and 7.5% HS exerts better protective effects, which is related to the inhibition of hippocampal neuronal apoptosis.
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tianbao
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yanan
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xi
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China.
authors.forename: He
authors.initials: H
authors.lastname: Jinhua
authors.affiliation: Department of Anesthesiology, The Third Hospital of Hebei Medical University, No 139, Ziqiang Road, Shijiazhuang City, 050051, Hebei, China. Electronic address: wangqiujunsjz@163.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Qiujun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D011183:Postoperative Complications / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D013156:Splenectomy; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C000617196:Bcl2 protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012462:Saline Solution, Hypertonic; D051028:bcl-2-Associated X Protein; D009553:Nimodipine
keywords: Cytoplasmic calcium; Hippocampus; Neuronal apoptosis; Post-operative cognition dysfunction