Biomarkers of brain injury in foals with hypoxic-ischemic encephalopathy.

Abstract

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (NHIE) is a disease affecting newborn foals for which there is no antemortem diagnostic test. HYPOTHESIS: Ubiquitin C-terminal hydrolase 1 (UCHL1) and the phosphorylated axonal forms of neurofilament H (pNF-H) are markers of brain injury in foals with NHIE. ANIMALS: Thirty-three foals with a clinical diagnosis consistent with NHIE and 17 healthy foals. METHODS: Retrospective study. Concentrations of UCHL1 and pNF-H in plasma were measured by ELISA. The performance of the assays for the diagnosis of NHIE was assessed by receiver operating characteristic curve analysis. Concentrations of UCHL1 and pNF-H were measured throughout the brains of 2 healthy foals. RESULTS: The diagnostic performance of UCHL1 (AUC = 0.86) was significantly higher (P = .001) than that of pNF-H (0.52) for the diagnosis of NHIE. Median concentrations of UCHL1 (6.57 ng/mL; 2.35-11.90 ng/mL) in foals with a clinical diagnosis of NHIE were significantly (P < .001) higher than those of healthy controls (2.52 ng/mL; 1.4-4.01 ng/mL). The right sided reference interval for UCHL1 concentrations in healthy foals was 0-4.01 ng/mL. The sensitivity and specificity of UCHL1 (>4.01 ng/mL) for diagnosis of NHIE were 70% (51-84%) and 94% (72-99%), respectively. UCHL1 concentrations were higher in gray than white matter, while pNF-H concentrations were higher in white than gray matter. CONCLUSIONS AND CLINICAL IMPORTANCE: UCHL1 has potential as a marker of brain injury in foals with NHIE.