TY - JOUR
T1 - Serum levels of neuron-specific ubiquitin carboxyl-terminal esterase-L1 predict brain injury in a canine model of hypothermic circulatory arrest
AU - Arnaoutakis, George J.
AU - George, Timothy J.
AU - Wang, Kevin K.
AU - Wilson, Mary Ann
AU - Allen, Jeremiah G.
AU - Robinson, Chase W.
AU - Haggerty, Kara A.
AU - Weiss, Eric S.
AU - Blue, Mary E.
AU - Talbot, Charles C.
AU - Troncoso, Juan C.
AU - Johnston, Michael V.
AU - Baumgartner, William A.
N1 - Funding Information:
Disclosures: Dr Wang owns stock and is an executive officer of Banyan Biomarkers, Inc, and as such may benefit financially as a result of the outcomes of this research or the work reported in this publication. This study was supported by the National Institutes of Health ( NIH RO1 HL091541-18 WAB and 1T32 CA126607-01A2 to G.J.A. ). Drs Arnaoutakis and Weiss are the Irene Piccinini Investigators in Cardiac Surgery and Drs George and Allen are the Hugh R. Sharp Cardiac Surgery Research Fellows.
PY - 2011/10
Y1 - 2011/10
N2 - Objectives: Ubiquitin carboxyl-terminal esterase-L1 (UCHL1) is a protein highly selectively expressed in neurons and has been linked to neurodegenerative disease in humans. We hypothesize that UCHL1 would be an effective serum biomarker for brain injury as tested in canine models of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Methods: Dogs were exposed to CPB (n = 14), 1 hour of HCA (1h-HCA; n = 11), or 2 hours of HCA (2h-HCA; n = 20). Cerebrospinal fluid and serum were collected at baseline, 8 hours, and 24 hours after treatment. UCHL1 levels were measured using a sandwich enzyme-linked immunosorbent assay. Neurologic function and histopathology were scored at 24 hours, and UCHL1 immunoreactivity was examined at 8 hours. Results: Baseline UCHL1 protein levels in cerebrospinal fluid and serum were similar for all groups. In serum, UCHL1 levels were elevated at 8 hours after treatment for 2h-HCA subjects compared with baseline values (P < .01) and also compared with CPB dogs at 8 hours (P < .01). A serum UCHL1 level above 3.9 ng/(mg total protein) at 8 hours had the best discriminatory power for predicting functional disability. In cerebrospinal fluid, UCHL1 was elevated in all groups at 8 hours after treatment compared with baseline (P < .01). However, UCHL1 levels in cerebrospinal fluid remained elevated at 24 hours only in 2h-HCA subjects (P < .01). Functional and histopathologic scores were closely correlated (Pearson coefficient, 0.66; P < .01) and were significantly worse in 2h-HCA animals. Conclusions: This is the first report associating elevated serum UCHL1 with brain injury. The novel neuronal biomarker UCHL1 is increased in serum 8 hours after severe neurologic insult in 2h-HCA animals compared with CPB animals. These results support the potential for use in cardiac surgery patients and form the basis for clinical correlation in humans.
AB - Objectives: Ubiquitin carboxyl-terminal esterase-L1 (UCHL1) is a protein highly selectively expressed in neurons and has been linked to neurodegenerative disease in humans. We hypothesize that UCHL1 would be an effective serum biomarker for brain injury as tested in canine models of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Methods: Dogs were exposed to CPB (n = 14), 1 hour of HCA (1h-HCA; n = 11), or 2 hours of HCA (2h-HCA; n = 20). Cerebrospinal fluid and serum were collected at baseline, 8 hours, and 24 hours after treatment. UCHL1 levels were measured using a sandwich enzyme-linked immunosorbent assay. Neurologic function and histopathology were scored at 24 hours, and UCHL1 immunoreactivity was examined at 8 hours. Results: Baseline UCHL1 protein levels in cerebrospinal fluid and serum were similar for all groups. In serum, UCHL1 levels were elevated at 8 hours after treatment for 2h-HCA subjects compared with baseline values (P < .01) and also compared with CPB dogs at 8 hours (P < .01). A serum UCHL1 level above 3.9 ng/(mg total protein) at 8 hours had the best discriminatory power for predicting functional disability. In cerebrospinal fluid, UCHL1 was elevated in all groups at 8 hours after treatment compared with baseline (P < .01). However, UCHL1 levels in cerebrospinal fluid remained elevated at 24 hours only in 2h-HCA subjects (P < .01). Functional and histopathologic scores were closely correlated (Pearson coefficient, 0.66; P < .01) and were significantly worse in 2h-HCA animals. Conclusions: This is the first report associating elevated serum UCHL1 with brain injury. The novel neuronal biomarker UCHL1 is increased in serum 8 hours after severe neurologic insult in 2h-HCA animals compared with CPB animals. These results support the potential for use in cardiac surgery patients and form the basis for clinical correlation in humans.
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U2 - 10.1016/j.jtcvs.2011.06.027
DO - 10.1016/j.jtcvs.2011.06.027
M3 - Article
C2 - 21924148
AN - SCOPUS:80052867974
SN - 0022-5223
VL - 142
SP - 902-910.e1
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 4
ER -