title: Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.
abstract: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity.
  
  
  
  To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test.
  
  
  
  The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p < 0.05) but not in the CA1 region (p > 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age.
  
  
  
  Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.
authors.affiliation: Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan, China. mengjinhai2616@163.com.
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Cao
authors.forename: S
authors.initials: S
authors.lastname: Qu
authors.forename: S-S
authors.initials: SS
authors.lastname: Ma
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: L-Q
authors.initials: LQ
authors.lastname: Deng
authors.forename: W-J
authors.initials: WJ
authors.lastname: Yuan
authors.forename: J-H
authors.initials: JH
authors.lastname: Meng
mesh_terms: D000818:Animals; D001921:Brain; D019194:Ischemic Preconditioning; D007649:Ketamine; D051379:Mice; D000066829:Neuroprotection; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007649:Ketamine