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DOI: 10.1055/s-0031-1271773
© 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
Publication History
received August 19, 2010
accepted after revision December 11, 2010
Publication Date:
24 February 2011 (online)
![](https://www.thieme-connect.de/media/ejps/201103/lookinside/thumbnails/10.1055-s-0031-1271773-1.jpg)
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.
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.
Key words
deep hypothermic low flow (DHLF) - cerebral protection - PI3K/Akt signaling pathway - Akt1mutant mice
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Correspondence
Dr. Xuming Mo
Department of Cardiothoracic
Surgery
Nanjing Children's Hospital
Nanjing Medical University
72 Guangzhou Road
210008 Nanjing
China
Phone: +38 25 83114234
Fax: +38 25 83304239
Email: zhifeimawy@gmail.com