Glutamate excitotoxicity mediates neuronal apoptosis after hypothermic circulatory arrest.

The Annals of Thoracic Surgery
Elaine E TsengWilliam A Baumgartner

Abstract

Prolonged hypothermic circulatory arrest results in neuronal cell death and neurologic injury. We have previously shown that hypothermic circulatory arrest causes both neuronal apoptosis and necrosis in a canine model. Inhibition of neuronal nitric oxide synthase reduced neuronal apoptosis, while glutamate receptor antagonism reduced necrosis in our model. This study was undertaken to determine whether glutamate receptor antagonism reduces nitric oxide formation and neuronal apoptosis after hypothermic circulatory arrest. Sixteen hound dogs underwent 2 hours of circulatory arrest at 18 degrees C and were sacrificed after 8 hours. Group 1 (n = 8) was treated with MK-801, 0.75 mg/kg intravenously prior to arrest followed by 75 microg/kg/hour infusion. Group 2 dogs (n = 8) received vehicle only. Intracerebral levels of excitatory amino acids and citrulline, an equal coproduct of nitric oxide, were measured. Apoptosis, identified by hematoxylin and eosin staining and confirmed by electron microscopy, was blindly scored from 0 (normal) to 100 (severe injury), while nick-end labeling demonstrated DNA fragmentation. Dogs in groups 1 and 2 had similar intracerebral levels of glutamate. However, MK-801 significantly reduced intracerebra...Continue Reading

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Citations

Apr 5, 2014·The Journal of Thoracic and Cardiovascular Surgery·Jae-Kwang ShimG Burkhard Mackensen
Apr 30, 2013·Neurological Research·William A LiYuchuan Ding
Oct 27, 2016·International Journal of Molecular Sciences·Chao ZhangKeming Yun
Dec 31, 2016·International Journal of Molecular Sciences·Salazar JonesXiaofeng Jia
Jul 16, 2020·Biomolecules & Therapeutics·Buyun KimByoungduck Park
Dec 22, 2020·The Journal of Surgical Research·Katherine GiulianoJennifer Lawton
Feb 11, 2020·The Journal of Thoracic and Cardiovascular Surgery·Masaki KajimotoMichael A Portman
Jun 2, 2021·Journal of Cardiothoracic Surgery·Michael R BoswellW Michael Hooten

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