Biomarkers of brain injury in foals with hypoxic-ischemic encephalopathy

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.