title: Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer's disease.
abstract: OBJECTIVE
  Autopsy evidence suggests that the presence of both Alzheimer(')s disease (AD) and cerebral infarction pathology is associated with more severe cognitive impairment than that produced by AD pathology alone. This study aims to investigate the effect of cerebral ischemia on cognitive function in rats with AD constructed by hippocampal injection and to determine its underlying mechanism, which is proposed to be of significance to the treatment of AD.
  
  
  METHODS
  AD was modeled by injection of aggregated Aβ(1-40), either alone or followed by hippocampal endothelin-1 injection to mimic cerebral ischemia in hippocampus, into the right dentate gyrus (DG) of rats. The Morris water maze was used to evaluate cognitive function. Aβ deposition, neuronal loss and phosphorylated tau expression in hippocampus were examined by Congo red staining, Nissl's staining and immunohistochemistry, respectively. Reactive astrocytes, IL-1β and TNF-α expressions were measured by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Compared with rats treated with either Aβ or endothelin alone, rats treated with both Aβ and endothelin showed more aggravated cognitive impairment and more Aβ deposits, neuron loss, phosphorylated tau expression, reactive astrocytes, IL-1β and TNF-α expressions in hippocampus.
  
  
  CONCLUSIONS
  Hippocampal ischemia aggravates cognitive impairment of AD rats by increasing Aβ deposits, neuron loss and tau phosphorylation in hippocampus. The enhanced inflammatory response may be responsible for cerebral ischemia-induced aggravation of cognitive impairment in AD rats. Based on these findings, prevention and treatment of cerebral ischemia may improve clinical symptoms of AD and suppress the progression of AD.
authors.affiliation: Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yan-Jiang
authors.initials: YJ
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Chuan-Qin
authors.initials: CQ
authors.lastname: Fang
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Zhou
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D003072:Cognition Disorders / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019332:Endothelin-1 / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019332:Endothelin-1; D053583:Interleukin-1beta; D016328:NF-kappa B; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40); D016875:tau Proteins