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Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity
BACKGROUND: Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349693/ https://www.ncbi.nlm.nih.gov/pubmed/25738507 http://dx.doi.org/10.1371/journal.pone.0115045 |
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author | Morales, Diego M. Holubkov, Richard Inder, Terri E. Ahn, Haejun C. Mercer, Deanna Rao, Rakesh McAllister, James P. Holtzman, David M. Limbrick, David D. |
author_facet | Morales, Diego M. Holubkov, Richard Inder, Terri E. Ahn, Haejun C. Mercer, Deanna Rao, Rakesh McAllister, James P. Holtzman, David M. Limbrick, David D. |
author_sort | Morales, Diego M. |
collection | PubMed |
description | BACKGROUND: Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment. OBJECTIVE: The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH. METHODS: CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses. RESULTS: CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95). CONCLUSIONS: Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant. |
format | Online Article Text |
id | pubmed-4349693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43496932015-03-17 Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity Morales, Diego M. Holubkov, Richard Inder, Terri E. Ahn, Haejun C. Mercer, Deanna Rao, Rakesh McAllister, James P. Holtzman, David M. Limbrick, David D. PLoS One Research Article BACKGROUND: Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment. OBJECTIVE: The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH. METHODS: CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses. RESULTS: CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95). CONCLUSIONS: Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant. Public Library of Science 2015-03-04 /pmc/articles/PMC4349693/ /pubmed/25738507 http://dx.doi.org/10.1371/journal.pone.0115045 Text en © 2015 Morales et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Morales, Diego M. Holubkov, Richard Inder, Terri E. Ahn, Haejun C. Mercer, Deanna Rao, Rakesh McAllister, James P. Holtzman, David M. Limbrick, David D. Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title | Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title_full | Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title_fullStr | Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title_full_unstemmed | Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title_short | Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity |
title_sort | cerebrospinal fluid levels of amyloid precursor protein are associated with ventricular size in post-hemorrhagic hydrocephalus of prematurity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349693/ https://www.ncbi.nlm.nih.gov/pubmed/25738507 http://dx.doi.org/10.1371/journal.pone.0115045 |
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