Ribal S Darwish1, Nana S Amiridze. 1. Department of Anesthesiology, Critical Care Medicine Division, University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD 21201-1595, USA. Rdarwish@anes.umm.edu
Abstract
BACKGROUND: The intrinsic pathway of apoptosis has been proposed as one mechanism of cell death after traumatic brain injury (TBI). This study tested the hypothesis that cytochrome c and activated caspase-9 are released into the cerebrospinal fluid (CSF) after severe TBI and that their presence correlates with mitochondrial injury and severity of neurologic outcome. METHODS: Nine adult patients with severe TBI (GCS < or = 8) underwent placement of intraventricular catheters for monitoring and management of intracranial pressure. CSF was sampled at catheter insertion (2-26 h after injury) and at intervals of 24, 48, and 72 h thereafter. Control samples were obtained from patients undergoing spinal anesthesia (ASA1). CSF levels of cytochrome c and activated caspase-9 were measured using ELISA. RESULTS: Cytochrome c was detected in 18 (51.4%) samples, in the range of 0.08-5 ng/ml; mean value for cytochrome c was 0.44 ng/ml (SD +/- 0.632). Activated caspase-9 was detected in 10 samples (28.6%); mean value was 0.28 ng/ml (SD +/- 0.39). R (s) between cytochrome c and Glasgow outcome score (GOS) was -0.25 (P = 0.14), and between GOS and activated caspase-9 was -0.35 (P = 0.04). R calculated based on linear regression of activated caspase-9 and cytochrome c concentrations was 0.18. Control CSF samples had no detectable levels of either marker (detection level for cytochrome c was 0.08 ng/ml and 0.20 for activated caspase-9). CONCLUSIONS: We concluded that activated caspase-9 and cytochrome c are present in the CSF of patients with severe TBI. Activated caspase-9 shows weak correlation with poor neurologic outcome.
BACKGROUND: The intrinsic pathway of apoptosis has been proposed as one mechanism of cell death after traumatic brain injury (TBI). This study tested the hypothesis that cytochrome c and activated caspase-9 are released into the cerebrospinal fluid (CSF) after severe TBI and that their presence correlates with mitochondrial injury and severity of neurologic outcome. METHODS: Nine adult patients with severe TBI (GCS < or = 8) underwent placement of intraventricular catheters for monitoring and management of intracranial pressure. CSF was sampled at catheter insertion (2-26 h after injury) and at intervals of 24, 48, and 72 h thereafter. Control samples were obtained from patients undergoing spinal anesthesia (ASA1). CSF levels of cytochrome c and activated caspase-9 were measured using ELISA. RESULTS:Cytochrome c was detected in 18 (51.4%) samples, in the range of 0.08-5 ng/ml; mean value for cytochrome c was 0.44 ng/ml (SD +/- 0.632). Activated caspase-9 was detected in 10 samples (28.6%); mean value was 0.28 ng/ml (SD +/- 0.39). R (s) between cytochrome c and Glasgow outcome score (GOS) was -0.25 (P = 0.14), and between GOS and activated caspase-9 was -0.35 (P = 0.04). R calculated based on linear regression of activated caspase-9 and cytochrome c concentrations was 0.18. Control CSF samples had no detectable levels of either marker (detection level for cytochrome c was 0.08 ng/ml and 0.20 for activated caspase-9). CONCLUSIONS: We concluded that activated caspase-9 and cytochrome c are present in the CSF of patients with severe TBI. Activated caspase-9 shows weak correlation with poor neurologic outcome.
Authors: R S Clark; P M Kochanek; S C Watkins; M Chen; C E Dixon; N A Seidberg; J Melick; J E Loeffert; P D Nathaniel; K L Jin; S H Graham Journal: J Neurochem Date: 2000-02 Impact factor: 5.372
Authors: Susan M Knoblach; Maria Nikolaeva; Xiuling Huang; Lei Fan; Stanislaw Krajewski; John C Reed; Alan I Faden Journal: J Neurotrauma Date: 2002-10 Impact factor: 5.269
Authors: W Ertel; M Keel; R Stocker; H G Imhof; M Leist; U Steckholzer; M Tanaka; O Trentz; S Nagata Journal: J Neuroimmunol Date: 1997-12 Impact factor: 3.478
Authors: Philipp M Lenzlinger; Andreas Marx; Otmar Trentz; Thomas Kossmann; Maria Cristina Morganti-Kossmann Journal: J Neuroimmunol Date: 2002-01 Impact factor: 3.478
Authors: Jianhua Qiu; Michael J Whalen; Pedro Lowenstein; Gary Fiskum; Brenda Fahy; Ribal Darwish; Bizhan Aarabi; Junying Yuan; Michael A Moskowitz Journal: J Neurosci Date: 2002-05-01 Impact factor: 6.167
Authors: Margaret A Satchell; Yichen Lai; Patrick M Kochanek; Stephen R Wisniewski; Ericka L Fink; Neal A Siedberg; Rachel P Berger; Steven T DeKosky; P David Adelson; Robert S B Clark Journal: J Cereb Blood Flow Metab Date: 2005-07 Impact factor: 6.200
Authors: Hülya Bayir; Patrick M Kochanek; Shang-Xi Liu; Antonio Arroyo; Anatoly Osipov; Jianfei Jiang; Stephan Wisniewski; P David Adelson; Steven H Graham; Valerian E Kagan Journal: J Cereb Blood Flow Metab Date: 2003-01 Impact factor: 6.200
Authors: Amy K Wagner; Krutika B Amin; Christian Niyonkuru; Brett A Postal; Emily H McCullough; Haishin Ozawa; C Edward Dixon; Hulya Bayir; Robert S Clark; Patrick M Kochanek; Anthony Fabio Journal: J Cereb Blood Flow Metab Date: 2011-03-30 Impact factor: 6.200
Authors: Erik Su; Michael J Bell; Stephen R Wisniewski; P David Adelson; Keri L Janesko-Feldman; Rosanne Salonia; Robert S B Clark; Patrick M Kochanek; Valerian E Kagan; Hülya Bayır Journal: Dev Neurosci Date: 2010-12-02 Impact factor: 2.984
Authors: Alicia K Au; Rajesh K Aneja; Michael J Bell; Hülya Bayir; Keri Feldman; P David Adelson; Ericka L Fink; Patrick M Kochanek; Robert S B Clark Journal: J Neurotrauma Date: 2012-04-27 Impact factor: 5.269
Authors: Chrystian J Alves; Rafael Dariolli; Frederico M Jorge; Matheus R Monteiro; Jessica R Maximino; Roberto S Martins; Bryan E Strauss; José E Krieger; Dagoberto Callegaro; Gerson Chadi Journal: Front Cell Neurosci Date: 2015-08-04 Impact factor: 5.505