title: Cerebroprotective effects of ibuprofen on diabetic encephalopathy in rats.
abstract: OBJECTIVE
  Diabetic encephalopathy is characterised by cognitive impairment, neurochemical and structural abnormalities. The aim of the study was to investigate the effects of ibuprofen on diabetic encephalopathy and potential mechanisms.
  
  
  METHODS
  Diabetes was induced through a single intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic rats were treated with ibuprofen (40 mg/kg) by gavage for 8 weeks. Cognitive performances were evaluated using Morris water maze. The temporal cortex and hippocampus were obtained to evaluate the levels of advanced glycation endproducts (AGEs) and their receptor (RAGE), the activity, protein expression, and mRNA levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), the protein and mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), and the protein expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Blood was obtained for the evaluation of interleukin 1β level.
  
  
  RESULTS
  Chronic ibuprofen treatment significantly prevented the decline in learning and memory ability of diabetic rats and loss of neurons in the CA1 and CA3 areas of the hippocampus. Moreover, ibuprofen treatment markedly reduced the activity, protein, and mRNA levels of BACE1, AGE level, protein expression of RAGE, COX-2, and iNOS in the brain, and interleukin 1β level in serum, while increasing the protein and mRNA expression of PPARγ in the brain of diabetic rats. However, ibuprofen had no effects on the hyperglycaemia and the body weight of diabetic rats.
  
  
  CONCLUSIONS
  These findings demonstrated that ibuprofen markedly ameliorated diabetic encephalopathy, potentially reflecting the down-regulation of BACE1, the suppression of the AGE/RAGE axis, and the anti-inflammation in diabetic rat brain.
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, Jiangsu, China.
authors.forename: Yao-Wu
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, Jiangsu, China. Electronic address: yinxx@xzmc.edu.cn.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D001927:Brain Diseases / Q000150:complications / Q000188:drug therapy*; D017931:DNA Primers; D048909:Diabetes Complications / Q000188:drug therapy*; D007052:Ibuprofen / Q000627:therapeutic use*; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D018696:Neuroprotective Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D007052:Ibuprofen
keywords: Advanced glycation endproducts; Diabetic encephalopathy; Ibuprofen; Inflammation; Peroxisome proliferator-activated receptor γ; β-amyloid precursor protein cleaving enzyme 1