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 5 0.86) was significantly higher (P 5 .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 o .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 (44.01 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.

Hypoxic Ischemic Encephalopathy—What Can We Learn from Humans?

“…A recent article investigating biomarkers of brain injury in foals with HIE described the pathologic findings of 3 foals that had performed histopathology. There was neuronal necrosis of the gray matter of the cerebral cortex, caudate nuclei, thalamus, hippocampus, cerebellar cortex, and medulla oblongata, which was consistent with a diagnosis of hypoxic ischemic brain injury …”

Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis

“…A second generation pNF-H assay, using a novel monoclonal pNF-H capture antibody screened originally by ability to capture pNF-H from concentrated protein solutions, has also been described and is marketed by EnCor Biotechnology (M α -pNF-H ELISA) [39]. These ELISA methods have been used to measure pNF-H in serum in several neurological conditions including aneurysmal subarachnoid haemorrhage [40], amyotrophic lateral sclerosis [39], Leber's hereditary optic neuropathy [41], and neonatal hypoxic-ischemic encephalopathy [42, 43], but no publication has as yet described the use of this assay on plasma or serum samples from MS patients. …”

Factors Associated With Nonsurvival in Foals Diagnosed With Perinatal Asphyxia Syndrome

“…Recent studies have shown that neurobiomarkers [6,7,8,9] may be useful indicators of neural tissue compromise in foals.…”