title: Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain.
abstract: BACKGROUND
  Activation of N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors play an important role in the neurons death induced by ischemia. The mitigating effect of intravenous anesthetics on ischemic neuron injury is related to their influence on NMDA receptors. This study was performed to investigate the effect of ketamine-midazolam anesthesia on the NMDA and AMPA receptor subunits expression in the peri-infarction of ischemic rat brain and explore its potential mechanism of neuroprotection.
  
  
  METHODS
  Thirty Sprague Dawley (SD) rats were subjected to permanent middle cerebral artery occlusion under ketamine/atropine (100/0.05 mg/kg) or ketamine-midazolam/atropine (60/50/0.05 mg/kg) intraperitoneal anesthesia (n=15 each). Twenty-four hours after ischemia, five rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally and infarct size was measured. Twenty-four and 72 hours after ischemia, four rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally. After staining the brain tissue slices with toluidine blue, the survived neurons in the peri-infarction were observed. Also, the expression level of NMDA receptors 1 (NR1), NMDA receptors 2A (NR2A), NMDA receptors 2B (NR2B) and AMPA (GluR1 subunit) were determined by grayscale analysis in immunohistochemical stained slices.
  
  
  RESULTS
  Compared with ketamine anesthesia, ketamine-midazolam anesthesia produced not only smaller infarct size [(24.1+/-4.6)% vs (38.4+/-4.2)%, P<0.05], but also higher neuron density (24 hours: 846+/-16 vs 756+/-24, P<0.05; 72 hours: 882+/-22 vs 785+/-18, P<0.05) and lower NR2A (24 hours: 123.0+/-4.9 vs 95.0+/-2.5, P<0.05; 72 hours: 77.8+/-4.1 vs 54.2+/-3.9, P<0.05) and NR2B (24 hours: 98.5+/-2.7 vs 76.3+/-2.4, P<0.05; 72 hours: 67.2 +/-7.5 vs 22.2+/-2.6, P<0.05) expression level in the peri-infarction following ischemia.
  
  
  CONCLUSIONS
  The protective effects of ketamine-midazolam anesthesia on ischemic brain injury may related to decreasing NR2A and NR2B expression.
authors.affiliation: Department of Neuroantomy and Histology Embryology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. zhangyuelin@sohu.com
authors.forename: Yue-lin
authors.initials: YL
authors.lastname: Zhang
authors.forename: Peng-bo
authors.initials: PB
authors.lastname: Zhang
authors.forename: Shu-dong
authors.initials: SD
authors.lastname: Qiu
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying-fang
authors.initials: YF
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000778:Anesthetics, Dissociative / Q000008:administration & dosage; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications; D007150:Immunohistochemistry; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D021122:Protein Subunits / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D008874:Midazolam