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Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats

Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the po...

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Autores principales: Rey-Funes, Manuel, Contartese, Daniela S., Peláez, Rafael, García-Sanmartín, Josune, Narro-Íñiguez, Judit, Soliño, Manuel, Fernández, Juan Carlos, Sarotto, Aníbal, Ciranna, Nicolás S., López-Costa, Juan José, Dorfman, Verónica B., Larrayoz, Ignacio M., Loidl, C. Fabián, Martínez, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060653/
https://www.ncbi.nlm.nih.gov/pubmed/33897437
http://dx.doi.org/10.3389/fphar.2021.651599
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author Rey-Funes, Manuel
Contartese, Daniela S.
Peláez, Rafael
García-Sanmartín, Josune
Narro-Íñiguez, Judit
Soliño, Manuel
Fernández, Juan Carlos
Sarotto, Aníbal
Ciranna, Nicolás S.
López-Costa, Juan José
Dorfman, Verónica B.
Larrayoz, Ignacio M.
Loidl, C. Fabián
Martínez, Alfredo
author_facet Rey-Funes, Manuel
Contartese, Daniela S.
Peláez, Rafael
García-Sanmartín, Josune
Narro-Íñiguez, Judit
Soliño, Manuel
Fernández, Juan Carlos
Sarotto, Aníbal
Ciranna, Nicolás S.
López-Costa, Juan José
Dorfman, Verónica B.
Larrayoz, Ignacio M.
Loidl, C. Fabián
Martínez, Alfredo
author_sort Rey-Funes, Manuel
collection PubMed
description Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery. Four experimental groups were studied: Rats born naturally as controls (CTL), animals that were exposed to PA for 20 min at 37°C (PA), animals exposed to PA for 20 min at 15°C (HYP), and animals that were exposed to PA for 20 min at 37°C and, immediately after birth, kept for 15 min at 8°C (HYP-PA). To evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 45 days of age. Molecular (real time PCR) and histological (immunohistochemistry, immunofluorescence, TUNEL assay) techniques were applied to the eyes of all experimental groups collected at 6, 12, 24, and 48 h, and 6 days after birth. PA resulted in a significant reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram. All animals treated with hypothermia had a significant correction of the a-wave and OP, but the b-wave was fully corrected in the HYP group but only partially in the HYP-PA group. The number of TUNEL-positive cells increased sharply in the ganglion cell layer of the PA animals and this increase was significantly prevented by both hypothermia treatments. Expression of the cold-shock proteins, cold-inducible RNA binding protein (CIRP) and RNA binding motif protein 3 (RBM3), was undetectable in retinas of the CTL and PA groups, but they were highly expressed in ganglion neurons and cells of the inner nuclear layer of the HYP and HYP-PA groups. In conclusion, our results suggest that a post-partum hypothermic shock could represent a useful and affordable method to prevent asphyxia-related vision disabling sequelae.
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spelling pubmed-80606532021-04-23 Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats Rey-Funes, Manuel Contartese, Daniela S. Peláez, Rafael García-Sanmartín, Josune Narro-Íñiguez, Judit Soliño, Manuel Fernández, Juan Carlos Sarotto, Aníbal Ciranna, Nicolás S. López-Costa, Juan José Dorfman, Verónica B. Larrayoz, Ignacio M. Loidl, C. Fabián Martínez, Alfredo Front Pharmacol Pharmacology Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery. Four experimental groups were studied: Rats born naturally as controls (CTL), animals that were exposed to PA for 20 min at 37°C (PA), animals exposed to PA for 20 min at 15°C (HYP), and animals that were exposed to PA for 20 min at 37°C and, immediately after birth, kept for 15 min at 8°C (HYP-PA). To evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 45 days of age. Molecular (real time PCR) and histological (immunohistochemistry, immunofluorescence, TUNEL assay) techniques were applied to the eyes of all experimental groups collected at 6, 12, 24, and 48 h, and 6 days after birth. PA resulted in a significant reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram. All animals treated with hypothermia had a significant correction of the a-wave and OP, but the b-wave was fully corrected in the HYP group but only partially in the HYP-PA group. The number of TUNEL-positive cells increased sharply in the ganglion cell layer of the PA animals and this increase was significantly prevented by both hypothermia treatments. Expression of the cold-shock proteins, cold-inducible RNA binding protein (CIRP) and RNA binding motif protein 3 (RBM3), was undetectable in retinas of the CTL and PA groups, but they were highly expressed in ganglion neurons and cells of the inner nuclear layer of the HYP and HYP-PA groups. In conclusion, our results suggest that a post-partum hypothermic shock could represent a useful and affordable method to prevent asphyxia-related vision disabling sequelae. Frontiers Media S.A. 2021-04-08 /pmc/articles/PMC8060653/ /pubmed/33897437 http://dx.doi.org/10.3389/fphar.2021.651599 Text en Copyright © 2021 Rey-Funes, Contartese, Peláez, García-Sanmartín, Narro-Íñiguez, Soliño, Fernández, Sarotto, Ciranna, López-Costa, Dorfman, Larrayoz, Loidl and Martínez. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Rey-Funes, Manuel
Contartese, Daniela S.
Peláez, Rafael
García-Sanmartín, Josune
Narro-Íñiguez, Judit
Soliño, Manuel
Fernández, Juan Carlos
Sarotto, Aníbal
Ciranna, Nicolás S.
López-Costa, Juan José
Dorfman, Verónica B.
Larrayoz, Ignacio M.
Loidl, C. Fabián
Martínez, Alfredo
Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title_full Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title_fullStr Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title_full_unstemmed Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title_short Hypothermic Shock Applied After Perinatal Asphyxia Prevents Retinal Damage in Rats
title_sort hypothermic shock applied after perinatal asphyxia prevents retinal damage in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060653/
https://www.ncbi.nlm.nih.gov/pubmed/33897437
http://dx.doi.org/10.3389/fphar.2021.651599
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