Increased cytochrome c in rat cerebrospinal fluid after cardiac arrest and its effects on hypoxic neuronal survival

RESUSCITATION

卷:83

Article

Liu, Hao^1,2  Sarnaik, Syana M.³  Manole, Mioara D.³  Chen, Yaming^4,5  Shinde, Sunita N.²  Li, Wenjin^1,2  Rose, Marie^1,2  Alexander, Henry⁵  Chen, Jie²  Clark, Robert S. B.^4,5  Graham, Steven H.^1,2  Hickey, Robert W.³ 

[1] VA Pittsburgh Healthcare Ctr, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA

[2] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA

[4] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA

[5] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA

关键词: Cerebrospinal fluid;    Brain ischemia;    Cardiac arrest;    Cytochrome c;   

DOI  :  10.1016/j.resuscitation.2012.04.009

来源: Elsevier

【 摘 要 】

Cerebrospinal fluid (CSF) proteins may be useful biomarkers of neuronal death and ultimate prognosis after hypoxic-ischemic brain injury. Cytochrome c has been identified in the CSF of children following traumatic brain injury. Cytochrome c is required for cellular respiration but it is also a central component of the intrinsic pathway of apoptosis. Thus, in addition to serving as a biomarker, cytochrome c release into CSF may have an effect upon survival of adjacent neurons. In this study, we use Western blot and ELISA to show that cytochrome c is elevated in CSF obtained from pediatric rats following resuscitation from cardiac arrest. Using biotinylated human cytochrome c in culture media we show that cytochrome c crosses the cell membrane and is incorporated into mitochondria of neurons exposed to anoxia. Lastly, we show that addition of human cytochrome c to primary neuronal culture exposed to anoxia improves survival. To our knowledge, this is the first study to show cytochrome c is elevated in CSF following hypoxic ischemic brain injury. Results from primary neuronal culture suggest that extracellular cytochrome c is able to cross the cell membrane of injured neurons, incorporate into mitochondria, and promote survival following anoxia. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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