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脱氢表雄酮和硫酸脱氢表雄酮在新生儿缺氧缺血性脑损伤中的作用。

Effects of DHEA and DHEAS in Neonatal Hypoxic-Ischemic Brain Injury.

作者信息

Mayer Elena, Winkler Ira, Huber Eva, Urbanek Martina, Kiechl-Kohlendorfer Ursula, Griesmaier Elke, Posod Anna

机构信息

Department of Pediatrics II (Neonatology), Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.

出版信息

Antioxidants (Basel). 2024 Dec 16;13(12):1542. doi: 10.3390/antiox13121542.

DOI:10.3390/antiox13121542
PMID:39765870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11726961/
Abstract

Neonatal brain injury remains a significant issue with limited treatment options. This study investigates the potential of the endogenous neurosteroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) as neuroprotective agents, building on evidence of their mechanisms in adult brain injury models. The primary objective was to evaluate their neuroprotective and anti-oxidative properties in a mouse model of neonatal hypoxic-ischemic brain injury. Using the modified Rice-Vannucci model, brain injury was induced in 7-day-old mouse pups, followed by treatment with various concentrations of DHEA and DHEAS (0.1, 1, and 10 µg/g body weight) via intraperitoneal injection after a 2 h recovery period. Mice were sacrificed after 24 hours for analysis of somatometry, brain injury, apoptosis, microglial activation, and oxidative stress markers (NOX2, 4-HNE, 8-OHdG), along with the anti-oxidant marker SOD1. While no statistically significant effects of DHEA or DHEAS were observed at the tested doses and time points, the absence of toxic or adverse effects highlights their safety profile. These findings provide a foundation for further research into optimizing dosing strategies, timing, and delivery methods. Future studies should refine these variables to maximize neuroprotective efficacy, investigate DHEA(S)' exact mechanisms of action, and explore their potential for clinical application in neonatal care.

摘要

新生儿脑损伤仍然是一个重大问题，治疗选择有限。本研究基于内源性神经甾体脱氢表雄酮（DHEA）及其硫酸酯（DHEAS）在成体脑损伤模型中的作用机制证据，探讨其作为神经保护剂的潜力。主要目的是在新生小鼠缺氧缺血性脑损伤模型中评估它们的神经保护和抗氧化特性。使用改良的Rice-Vannucci模型，在7日龄幼鼠中诱导脑损伤，在2小时恢复期后通过腹腔注射给予不同浓度的DHEA和DHEAS（0.1、1和10μg/g体重）。24小时后处死小鼠，分析躯体测量、脑损伤、细胞凋亡、小胶质细胞活化和氧化应激标志物（NOX2、4-HNE、8-OHdG）以及抗氧化标志物SOD1。虽然在所测试的剂量和时间点未观察到DHEA或DHEAS有统计学显著效应，但未出现毒性或不良反应突出了它们的安全性。这些发现为进一步研究优化给药策略、时间和给药方法奠定了基础。未来的研究应优化这些变量以最大化神经保护效果，研究DHEA（S）的确切作用机制，并探索它们在新生儿护理中的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/3c9e2ae9ddbf/antioxidants-13-01542-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/d1d052e67f30/antioxidants-13-01542-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/c87b156e4b07/antioxidants-13-01542-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/4484eecb6420/antioxidants-13-01542-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/5009217f77ba/antioxidants-13-01542-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/428d1255e8d9/antioxidants-13-01542-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/7204f9119248/antioxidants-13-01542-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/9f71a1b76d1f/antioxidants-13-01542-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/ee08266b7b2a/antioxidants-13-01542-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/3c9e2ae9ddbf/antioxidants-13-01542-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/d1d052e67f30/antioxidants-13-01542-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/c87b156e4b07/antioxidants-13-01542-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/4484eecb6420/antioxidants-13-01542-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/5009217f77ba/antioxidants-13-01542-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/428d1255e8d9/antioxidants-13-01542-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/7204f9119248/antioxidants-13-01542-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/9f71a1b76d1f/antioxidants-13-01542-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/ee08266b7b2a/antioxidants-13-01542-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e5/11726961/3c9e2ae9ddbf/antioxidants-13-01542-g009.jpg

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