title: Increased cytochrome c in rat cerebrospinal fluid after cardiac arrest and its effects on hypoxic neuronal survival.
abstract: 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.
authors.affiliation: Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare Center, PA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Syana M
authors.initials: SM
authors.lastname: Sarnaik
authors.forename: Mioara D
authors.initials: MD
authors.lastname: Manole
authors.forename: Yaming
authors.initials: Y
authors.lastname: Chen
authors.forename: Sunita N
authors.initials: SN
authors.lastname: Shinde
authors.forename: Wenjin
authors.initials: W
authors.lastname: Li
authors.forename: Marie
authors.initials: M
authors.lastname: Rose
authors.forename: Henry
authors.initials: H
authors.lastname: Alexander
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hickey
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D045304:Cytochromes c / Q000134:cerebrospinal fluid*; D006323:Heart Arrest / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D045304:Cytochromes c