Biomarkers of brain injury in foals with hypoxic-ischemic encephalopathy.
Abstract: Neonatal hypoxic-ischemic encephalopathy (NHIE) is a disease affecting newborn foals for which there is no antemortem diagnostic test. Objective: 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. Methods: 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 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: UCHL1 has potential as a marker of brain injury in foals with NHIE.
Copyright © 2010 by the American College of Veterinary Internal Medicine.
Publication Date: 2010-12-08 PubMed ID: 21143301DOI: 10.1111/j.1939-1676.2010.0645.xGoogle Scholar: Lookup
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- Journal Article
- Multicenter Study
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates potential biomarkers for diagnosing Hypoxic-Ischemic Encephalopathy (NHIE), a condition affecting newborn foals, leveraging ELISA tests for the Ubiquitin C-terminal hydrolase 1 (UCHL1) and phosphorylated axonal forms of neurofilament H (pNF-H). It is concluded that UCHL1 demonstrated greater diagnostic performance and reliability over pNF-H, hence, it could serve as a promising biomarker for NHIE.
Objectives and Methodology
- The research aims to identify a potent biomarker for NHIE, a disease that currently lacks any diagnostic test. The biomarkers under study were UCHL1 and pNF-H, associated with brain injuries.
- Thirty-three foals diagnosed clinically with NHIE and 17 healthy foals were evaluated in this retrospective study.
- The plasma levels of UCHL1 and pNF-H were measured using Enzyme-linked Immunosorbent Assay (ELISA), a commonly used laboratory test to detect and measure antibodies in blood.
- To assess how well these biomarkers could be used for diagnosing NHIE, a Receiver Operating Characteristic (ROC) curve analysis was conducted.
- Plasma concentrations of these biomarkers were also measured in the brains of 2 healthy foals to establish a reference.
Findings
- The diagnostic performance of UCHL1 was significantly higher than that of pNF-H, as indicated by the Area Under the Curve (AUC) values of 0.86 and 0.52, respectively.
- UCHL1 concentrations were found to be higher in the foals with NHIE compared to healthy foals. The specified right-sided reference interval for healthy foals was 0-4.01 ng/mL.
- The sensitivity (true positive rate) and specificity (true negative rate) of UCHL1 for diagnosing NHIE were quite notable at 70% and 94%, respectively.
- UCHL1 concentrations were higher in grey matter than in white matter, contrasting with pNF-H concentrations, which were higher in white matter than grey matter.
Conclusions
- The potential of UCHL1 as a biomarker for brain injury in foals with NHIE has been underscored in this study.
- The higher concentrations of UCHL1 in foals exhibiting NHIE, combined with its superior diagnostic performance and high sensitivity and specificity rates, position it as a reliable biomarker for detecting this disease.
Cite This Article
APA
Ringger NC, Giguère S, Morresey PR, Yang C, Shaw G.
(2010).
Biomarkers of brain injury in foals with hypoxic-ischemic encephalopathy.
J Vet Intern Med, 25(1), 132-137.
https://doi.org/10.1111/j.1939-1676.2010.0645.x Publication
Researcher Affiliations
- Countryside Equine Hospital, Louisville, TN, USA.
MeSH Terms
- Animals
- Animals, Newborn
- Biomarkers / blood
- Blotting, Western
- Brain Injuries / blood
- Brain Injuries / pathology
- Brain Injuries / veterinary
- Enzyme-Linked Immunosorbent Assay / veterinary
- Horse Diseases / blood
- Horse Diseases / diagnosis
- Horse Diseases / pathology
- Horses
- Hypoxia-Ischemia, Brain / blood
- Hypoxia-Ischemia, Brain / pathology
- Hypoxia-Ischemia, Brain / veterinary
- Neurofilament Proteins / blood
- ROC Curve
- Retrospective Studies
- Sensitivity and Specificity
- Statistics, Nonparametric
- Ubiquitin Thiolesterase / blood
Citations
This article has been cited 9 times.- Donnelly CG, Johnson AL, Reed S, Finno CJ. Cerebrospinal fluid and serum proteomic profiles accurately distinguish neuroaxonal dystrophy from cervical vertebral compressive myelopathy in horses. J Vet Intern Med 2023 Mar;37(2):689-696.
- Donnelly CG, Finno CJ. Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses. Equine Vet J 2023 Sep;55(5):884-890.
- Ok M, Naseri A, Ates MB, Ider M, Uney K, Sevinc M, Hatipoglu F, Yildiz R, Erturk A, Baspinar N, Iyigun SS. The Usefulness of Serum Brain Damage Biomarkers in Detection and Evaluation of Hypoxic Ischemic Encephalopathy in Calves with Perinatal Asphyxia. Animals (Basel) 2022 Nov 21;12(22).
- Ellero N, Lanci A, Baldassarro VA, Alastra G, Mariella J, Cescatti M, Castagnetti C, Giardino L. Study on NGF and VEGF during the Equine Perinatal Period-Part 2: Foals Affected by Neonatal Encephalopathy. Vet Sci 2022 Aug 26;9(9).
- Aleman M, Costa LRR, Crowe C, Kass PH. Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses. J Vet Intern Med 2018 Sep;32(5):1731-1739.
- Aleman M, Weich KM, Madigan JE. Survey of Veterinarians Using a Novel Physical Compression Squeeze Procedure in the Management of Neonatal Maladjustment Syndrome in Foals. Animals (Basel) 2017 Sep 5;7(9).
- Bianco AW, Moore GE, Taylor SD. Neonatal Encephalopathy in Calves Presented to a University Hospital. J Vet Intern Med 2017 Nov;31(6):1892-1899.
- Gresle MM, Butzkueven H, Shaw G. Neurofilament proteins as body fluid biomarkers of neurodegeneration in multiple sclerosis. Mult Scler Int 2011;2011:315406.
- Lv H, Wang Q, Liu F, Jin L, Ren P, Li L. A biochemical feedback signal for hypothermia treatment for neonatal hypoxic-ischemic encephalopathy: focusing on central nervous system proteins in biofluids. Front Pediatr 2024;12:1288853.
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