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Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy

INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neon...

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Autores principales: Toader, Alina Mihaela, Hoteiuc, Oana, Bidian, Cristina, Oltean, Dan-Daniel, Tabaran, Flaviu, Grad, Ovidiu, Clichici, Simona, Mitrea, Daniela Rodica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Iuliu Hatieganu University of Medicine and Pharmacy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118207/
https://www.ncbi.nlm.nih.gov/pubmed/34013191
http://dx.doi.org/10.15386/mpr-1903
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author Toader, Alina Mihaela
Hoteiuc, Oana
Bidian, Cristina
Oltean, Dan-Daniel
Tabaran, Flaviu
Grad, Ovidiu
Clichici, Simona
Mitrea, Daniela Rodica
author_facet Toader, Alina Mihaela
Hoteiuc, Oana
Bidian, Cristina
Oltean, Dan-Daniel
Tabaran, Flaviu
Grad, Ovidiu
Clichici, Simona
Mitrea, Daniela Rodica
author_sort Toader, Alina Mihaela
collection PubMed
description INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia–ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia–ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. OBJECTIVES: The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. METHODS: The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7(th) postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O(2) for 90 minutes) and some groups to hypothermia. RESULTS: In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon’s Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. CONCLUSION: The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment.
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spelling pubmed-81182072021-05-18 Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy Toader, Alina Mihaela Hoteiuc, Oana Bidian, Cristina Oltean, Dan-Daniel Tabaran, Flaviu Grad, Ovidiu Clichici, Simona Mitrea, Daniela Rodica Med Pharm Rep Original Research: Physiology INTRODUCTION: Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia–ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia–ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. OBJECTIVES: The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. METHODS: The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7(th) postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O(2) for 90 minutes) and some groups to hypothermia. RESULTS: In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon’s Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. CONCLUSION: The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment. Iuliu Hatieganu University of Medicine and Pharmacy 2021-04 2021-04-29 /pmc/articles/PMC8118207/ /pubmed/34013191 http://dx.doi.org/10.15386/mpr-1903 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Research: Physiology
Toader, Alina Mihaela
Hoteiuc, Oana
Bidian, Cristina
Oltean, Dan-Daniel
Tabaran, Flaviu
Grad, Ovidiu
Clichici, Simona
Mitrea, Daniela Rodica
Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title_full Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title_fullStr Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title_full_unstemmed Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title_short Neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
title_sort neuronal apoptosis can be prevented by the combined therapy with melatonin and hypothermia in a neonatal rat model of hypoxic-ischemic encephalopathy
topic Original Research: Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118207/
https://www.ncbi.nlm.nih.gov/pubmed/34013191
http://dx.doi.org/10.15386/mpr-1903
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