title: [Keap1-tat peptide attenuates oxidative stress damage in hippocampal CA1 region and learning and memory deficits following global cerebral ischemia].
abstract: OBJECTIVE
  To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron, as well as the effect on spacial learning and memory function following global cerebral ischemia.
  
  
  METHODS
  Adult male Sprague Dawley (SD) rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 15 min and randomly divided into five groups: sham, sham+Keap1-tat, ischemia/reperfusion (I/R), Keap1-tat peptide- and vehicle-administrated groups. For Keap1-tat or vehicle groups, the rats were treated with Keap1-tat (30, 50, 100 μg in 5 μL 0.9% saline) or the same volume vehicle by intracerebroventricular injection (icv) 30 min prior to ischemia. Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region. The spatial learning and memory function of the rats was evaluated using Morris water maze.
  
  
  RESULTS
  Compared with sham group, the number of surviving neurons in ischemia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P<0.05), while administration of Keap1-tat significantly decreased the damage following GCI (P<0.05), and the dose of 50 μg existed the most effective neuroprotective role. Furthermore, immunostaining intensity of 4-HNE and 8-OHdG, markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region. Of significant interest, the time of finding underwater platform in Keap1-tat group animals was significantly short, and after removing the platform, the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehicle and I/R group animals (P<0.05).
  
  
  CONCLUSIONS
  Keap1-tat peptide can effectively attenuate neuronal damage in hippocampal CA1 region and improve learning and memory function, which might bedue to the attenuation of oxidative stress caused by GCI.
authors.affiliation: Pathology Staff Room, Tangshan Vocational Technical College, Tangshan 063004, Hebei, China.
authors.forename: Jing-yi
authors.initials: JY
authors.lastname: Tu
authors.affiliation: Institute of Medical Research Center, North China University of Science and Technology, Tangshan 063000, Hebei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Tangshan Xiehe Hospital, Tangshan 063000, Hebei, China.
authors.forename: Shu-ling
authors.initials: SL
authors.lastname: Shang
authors.affiliation: Institute of Medical Research Center, North China University of Science and Technology, Tangshan 063000, Hebei, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Medical Research Center, North China University of Science and Technology, Tangshan 063000, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Institute of Medical Research Center, North China University of Science and Technology, Tangshan 063000, Hebei, China.
authors.forename: Rui-min
authors.initials: RM
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D018782:Maze Learning; D008568:Memory; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress; D010455:Peptides / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D018696:Neuroprotective Agents; D010455:Peptides