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Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats

Neonatal hypoxic-ischemic (HI) brain injury is associated with long-term neurological disorders, and protective strategies are presently scarce. Sodium 4-phenylbutyrate (4-PBA) reportedly acts as a chemical chaperone that alleviates endoplasmic reticulum (ER) stress, which plays a critical role in n...

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Autores principales: Wu, Ziyi, Niu, Jiayuan, Xue, Hang, Wang, Shuo, Zhao, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904702/
https://www.ncbi.nlm.nih.gov/pubmed/33643009
http://dx.doi.org/10.3389/fnbeh.2021.632143
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author Wu, Ziyi
Niu, Jiayuan
Xue, Hang
Wang, Shuo
Zhao, Ping
author_facet Wu, Ziyi
Niu, Jiayuan
Xue, Hang
Wang, Shuo
Zhao, Ping
author_sort Wu, Ziyi
collection PubMed
description Neonatal hypoxic-ischemic (HI) brain injury is associated with long-term neurological disorders, and protective strategies are presently scarce. Sodium 4-phenylbutyrate (4-PBA) reportedly acts as a chemical chaperone that alleviates endoplasmic reticulum (ER) stress, which plays a critical role in neurological diseases. The present study aimed to evaluate the neuroprotective effects of 4-PBA on HI-induced neonatal brain injury in a rat model, and to characterize possible underlying mechanisms. The HI brain injury model was established by ligating the left common carotid artery in 7-day-old rats, followed by exposure to 8% oxygen for 2 h. The 4-PBA or vehicle was administered by an intracerebroventricular injection 30 min before HI. The protein expression levels of ER stress markers (GRP78, ATF6, and CHOP) were detected by western blotting at 24 h after HI insult. The activation of cAMP-response element-binding protein (CREB) was evaluated by western blotting and immunofluorescence. TUNEL and Nissl staining were performed to detect the histomorphological changes in the hippocampal neurons at 24 h and 7 days, respectively, after HI injury. From days 29 to 34 after brain HI, rats underwent Morris water maze tests to assess cognitive functioning. The results showed that pretreatment with 4-PBA decreased HI-induced excessive ER stress and neuronal injury. Moreover, CREB activation might be involved in the beneficial effects of 4-PBA on HI-induced learning and memory deficits in rats. In conclusion, the present study suggested a potential therapeutic approach of ER stress inhibition in the treatment of neonatal HI brain injury.
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spelling pubmed-79047022021-02-26 Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats Wu, Ziyi Niu, Jiayuan Xue, Hang Wang, Shuo Zhao, Ping Front Behav Neurosci Neuroscience Neonatal hypoxic-ischemic (HI) brain injury is associated with long-term neurological disorders, and protective strategies are presently scarce. Sodium 4-phenylbutyrate (4-PBA) reportedly acts as a chemical chaperone that alleviates endoplasmic reticulum (ER) stress, which plays a critical role in neurological diseases. The present study aimed to evaluate the neuroprotective effects of 4-PBA on HI-induced neonatal brain injury in a rat model, and to characterize possible underlying mechanisms. The HI brain injury model was established by ligating the left common carotid artery in 7-day-old rats, followed by exposure to 8% oxygen for 2 h. The 4-PBA or vehicle was administered by an intracerebroventricular injection 30 min before HI. The protein expression levels of ER stress markers (GRP78, ATF6, and CHOP) were detected by western blotting at 24 h after HI insult. The activation of cAMP-response element-binding protein (CREB) was evaluated by western blotting and immunofluorescence. TUNEL and Nissl staining were performed to detect the histomorphological changes in the hippocampal neurons at 24 h and 7 days, respectively, after HI injury. From days 29 to 34 after brain HI, rats underwent Morris water maze tests to assess cognitive functioning. The results showed that pretreatment with 4-PBA decreased HI-induced excessive ER stress and neuronal injury. Moreover, CREB activation might be involved in the beneficial effects of 4-PBA on HI-induced learning and memory deficits in rats. In conclusion, the present study suggested a potential therapeutic approach of ER stress inhibition in the treatment of neonatal HI brain injury. Frontiers Media S.A. 2021-02-11 /pmc/articles/PMC7904702/ /pubmed/33643009 http://dx.doi.org/10.3389/fnbeh.2021.632143 Text en Copyright © 2021 Wu, Niu, Xue, Wang and Zhao. http://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 Neuroscience
Wu, Ziyi
Niu, Jiayuan
Xue, Hang
Wang, Shuo
Zhao, Ping
Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title_full Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title_fullStr Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title_full_unstemmed Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title_short Sodium 4-Phenylbutyrate Protects Hypoxic-Ischemic Brain Injury via Attenuating Endoplasmic Reticulum Stress in Neonatal Rats
title_sort sodium 4-phenylbutyrate protects hypoxic-ischemic brain injury via attenuating endoplasmic reticulum stress in neonatal rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904702/
https://www.ncbi.nlm.nih.gov/pubmed/33643009
http://dx.doi.org/10.3389/fnbeh.2021.632143
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