title: Genetic suppression of Akt1 activity aggravates cerebral ischemia/reperfusion injury after deep hypothermic low flow in transgenic mice.
abstract: OBJECTIVE
  We investigated the genetic role of the PI3K/Akt signaling pathway in Akt1 (+/-) mice after cerebral ischemia/reperfusion injury following post-surgery deep hypothermic low flow.
  
  
  METHODS
  3-week-old Akt1 (+/-) and wild-type C57/B6 mice were randomly and equally divided into sham-surgery and surgery groups. Surgery group mice were subjected to gradual body temperature reduction and bilateral common carotid artery occlusion for 120 min at 18.5 ± 0.5 °C, followed by artery reopening and rewarming. Occlusion was not performed in sham-surgery group animals. Regional cerebral blood flow was determined by laser Doppler flowmetry. Using reverse transcriptase-PCR, apoptotic assays, immunohistology, and Western blot analyses, we determined the apoptotic level of cerebral cells and the expression of Akt signaling pathway components.
  
  
  RESULTS
  Regional cerebral blood flow was decreased by ≥ 86% during bilateral common carotid artery occlusion. Akt1 (+/-) mice experienced showed mortality after 24 h of cerebral I/R, and displayed increased numbers of apoptotic cerebral cells and apoptotic protein expression levels. Western analysis revealed Akt1 hypoactivity, which led to less efficient apoptotic signaling pathway inhibition.
  
  
  CONCLUSIONS
  Akt1 suppresses the mitochondrial apoptosis signaling pathway, and Akt1 haplo-insufficiency exacerbates cerebral ischemia/reperfusion after deep hypothermic low flow conditions in mice. Akt may be a potential molecular therapeutic target for brain protection during surgery in congenital heart disease patients.
authors.affiliation: Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.forename: X
authors.initials: X
authors.lastname: Mo
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics; D007036:Hypothermia, Induced; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics*; D015398:Signal Transduction; D013489:Suppression, Genetic
chemical_list: C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt