Eur J Pediatr Surg 2011; 21(3): 171-177
DOI: 10.1055/s-0031-1271773
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Genetic Suppression of Akt1 Activity Aggravates Cerebral Ischemia/Reperfusion Injury After Deep Hypothermic Low Flow in Transgenic Mice

Z. Ma1 , X. Mo1 , Z. Yang2 , F. Chen1 , X. He1
  • 1Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China
  • 2Model Animal Research Center, Nanjing University, Nanjing, China
Further Information

Publication History

received August 19, 2010

accepted after revision December 11, 2010

Publication Date:
24 February 2011 (online)


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.

Conclusion: 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.


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Dr. Xuming Mo

Department of Cardiothoracic


Nanjing Children's Hospital

Nanjing Medical University

72 Guangzhou Road

210008 Nanjing


Phone: +38 25 83114234

Fax: +38 25 83304239