UCH-L1 and GFAP serum levels in neonates with hypoxic-ischemic encephalopathy: a single center pilot study

被引:45
作者
Douglas-Escobar, Martha V. [1 ,2 ]
Heaton, Shelley C. [3 ]
Bennett, Jeffrey [4 ]
Young, Linda J. [5 ]
Glushakova, Olena [6 ]
Xu, Xiaohui [7 ]
Barbeau, Daphna Yasova [1 ]
Rossignol, Candice [1 ]
Miller, Cindy [1 ]
Crow, Alissa M. Old [4 ]
Hayes, Ronald L. [6 ]
Weiss, Michael D. [1 ]
机构
[1] Univ Florida, Dept Pediat, Gainesville, FL USA
[2] Univ Calif San Francisco, Dept Pediat, 505 Parnassus Ave,Moffitt Room M 680, San Francisco, CA 94143 USA
[3] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA
[4] Univ Florida, Dept Radiol, Gainesville, FL 32610 USA
[5] Univ Florida, Dept Stat, Gainesville, FL 32611 USA
[6] Banyan Biomarkers Inc, Alachua, FL USA
[7] Univ Florida, Dept Biostat, Gainesville, FL USA
关键词
biomarkers; HIE; UCH-L1; GFAP; TRAUMATIC BRAIN-INJURY; C-TERMINAL HYDROLASE-L1; WHOLE-BODY HYPOTHERMIA; THERAPEUTIC HYPOTHERMIA; PERINATAL ASPHYXIA; BIOMARKERS; BLOOD; ELECTROENCEPHALOGRAM; PREDICTION; OUTCOMES;
D O I
10.3389/fneur.2014.00273
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: We examined two potential biomarkers of brain damage in hypoxic ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.? Study Design: Serum UCH-L1 and GFAP concentrations from HIE neonates (n=16) were compared to controls (n=11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design. Result: Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter. Conclusion: Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.
引用
收藏
页数:8
相关论文
共 43 条
[1]   Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy. [J].
Azzopardi, Denis V. ;
Strohm, Brenda ;
Edwards, A. David ;
Dyet, Leigh ;
Halliday, Henry L. ;
Juszczak, Edmund ;
Kapellou, Olga ;
Levene, Malcolm ;
Marlow, Neil ;
Porter, Emma ;
Thoresen, Marianne ;
Whitelaw, Andrew ;
Brocklehurst, Peter .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (14) :1349-1358
[2]  
Barkovich AJ, 1998, AM J NEURORADIOL, V19, P143
[3]  
Bayley N., 2019, BAYLEY SCALES INFANT
[4]   Elevated Serum Ubiquitin Carboxy-Terminal Hydrolase L1 Is Associated with Abnormal Blood-Brain Barrier Function after Traumatic Brain Injury [J].
Blyth, Brian J. ;
Farahvar, Arash ;
He, Hua ;
Nayak, Akshata ;
Yang, Cui ;
Shaw, Gerry ;
Bazarian, Jeffrey J. .
JOURNAL OF NEUROTRAUMA, 2011, 28 (12) :2453-2462
[5]   Term neonate prognoses after perinatal asphyxia: Contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients [J].
Boichot, Christophe ;
Walker, Paul M. ;
Durand, Christine ;
Grimaldi, Marianne ;
Chapuis, Severine ;
Gouyon, Jean B. ;
Brunotte, Francois .
RADIOLOGY, 2006, 239 (03) :839-848
[6]   A new neurological focus in neonatal intensive care [J].
Bonifacio, Sonia L. ;
Glass, Hannah C. ;
Peloquin, Susan ;
Ferriero, Donna M. .
NATURE REVIEWS NEUROLOGY, 2011, 7 (09) :485-494
[7]   Biokinetic Analysis of Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in Severe Traumatic Brain Injury Patient Biofluids [J].
Brophy, Gretchen M. ;
Mondello, Stefania ;
Papa, Linda ;
Robicsek, Steven A. ;
Gabrielli, Andrea ;
Tepas, Joseph, III ;
Buki, Andras ;
Robertson, Claudia ;
Tortella, Frank C. ;
Hayes, Ronald L. ;
Wang, Kevin K. W. .
JOURNAL OF NEUROTRAUMA, 2011, 28 (06) :861-870
[8]   Biomarkers for Severity of Neonatal Hypoxic-Ischemic Encephalopathy and Outcomes in Newborns Receiving Hypothermia Therapy [J].
Chalak, Lina F. ;
Sanchez, Pablo J. ;
Adams-Huet, Beverley ;
Laptook, Abbot R. ;
Heyne, Roy J. ;
Rosenfeld, Charles R. .
JOURNAL OF PEDIATRICS, 2014, 164 (03) :468-+
[9]   Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator [J].
Czeiter, Endre ;
Mondello, Stefania ;
Kovacs, Noemi ;
Sandor, Janos ;
Gabrielli, Andrea ;
Schmid, Kara ;
Tortella, Frank ;
Wang, Kevin K. W. ;
Hayes, Ronald L. ;
Barzo, Pal ;
Ezer, Erzsebet ;
Doczi, Tamas ;
Buki, Andras .
JOURNAL OF NEUROTRAUMA, 2012, 29 (09) :1770-1778
[10]   UCHL1 (PGP 9.5): Neuronal biomarker and ubiquitin system protein [J].
Day, Ian N. M. ;
Thompson, Rod J. .
PROGRESS IN NEUROBIOLOGY, 2010, 90 (03) :327-362