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Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats

Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH(1-24) on a collagenase-induc...

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Autores principales: Martins, Camila A., Neves, Laura Tartari, de Oliveira, Marina M. B. P., Bagatini, Pamela Brambilla, Barboza, Rafaela, Mestriner, Régis Gemerasca, Xavier, Léder Leal, Rasia-Filho, Alberto A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576182/
https://www.ncbi.nlm.nih.gov/pubmed/33082383
http://dx.doi.org/10.1038/s41598-020-74712-7
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author Martins, Camila A.
Neves, Laura Tartari
de Oliveira, Marina M. B. P.
Bagatini, Pamela Brambilla
Barboza, Rafaela
Mestriner, Régis Gemerasca
Xavier, Léder Leal
Rasia-Filho, Alberto A.
author_facet Martins, Camila A.
Neves, Laura Tartari
de Oliveira, Marina M. B. P.
Bagatini, Pamela Brambilla
Barboza, Rafaela
Mestriner, Régis Gemerasca
Xavier, Léder Leal
Rasia-Filho, Alberto A.
author_sort Martins, Camila A.
collection PubMed
description Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH(1-24) on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH(1-24) (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH(1-24) dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100β, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH(1-24). ACTH(1-24) could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.
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spelling pubmed-75761822020-10-21 Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats Martins, Camila A. Neves, Laura Tartari de Oliveira, Marina M. B. P. Bagatini, Pamela Brambilla Barboza, Rafaela Mestriner, Régis Gemerasca Xavier, Léder Leal Rasia-Filho, Alberto A. Sci Rep Article Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH(1-24) on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH(1-24) (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH(1-24) dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100β, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH(1-24). ACTH(1-24) could be further evaluated to determine its suitability for preclinical models of PVH in premature infants. Nature Publishing Group UK 2020-10-20 /pmc/articles/PMC7576182/ /pubmed/33082383 http://dx.doi.org/10.1038/s41598-020-74712-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Martins, Camila A.
Neves, Laura Tartari
de Oliveira, Marina M. B. P.
Bagatini, Pamela Brambilla
Barboza, Rafaela
Mestriner, Régis Gemerasca
Xavier, Léder Leal
Rasia-Filho, Alberto A.
Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title_full Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title_fullStr Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title_full_unstemmed Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title_short Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
title_sort neuroprotective effect of acth on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576182/
https://www.ncbi.nlm.nih.gov/pubmed/33082383
http://dx.doi.org/10.1038/s41598-020-74712-7
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