Association between cold-inducible RNA binding motif 3 and hypothermia effect in murine hypoxia-ischemia model measured by metabolic MRI.

IF 2 4区医学 Q2 DEVELOPMENTAL BIOLOGY

Developmental Neuroscience Pub Date : 2025-09-25 DOI:10.1159/000548626

Xiaodan Liu, Xiangning Jiang, Alkisti Mikrogeorgiou Capper, Nicholas Stewart, Will Byrne, Xiao Ji, Jacob Ellison, Duan Xu, Donna M Ferriero

{"title":"Association between cold-inducible RNA binding motif 3 and hypothermia effect in murine hypoxia-ischemia model measured by metabolic MRI.","authors":"Xiaodan Liu, Xiangning Jiang, Alkisti Mikrogeorgiou Capper, Nicholas Stewart, Will Byrne, Xiao Ji, Jacob Ellison, Duan Xu, Donna M Ferriero","doi":"10.1159/000548626","DOIUrl":null,"url":null,"abstract":"Introduction: The efficacy of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) is inconsistent, and the cause remains unclear. This study aimed to explore the role of cold stress protein in the TH-induced neuroprotection following hypoxia-ischemia (HI) using metabolic MRI.Methods: Postnatal day 10 (P10) mice underwent unilateral HI followed by treatments with therapeutic hypothermia (TH) or normothermia (NT). HI and sham mice were scanned at 4 h and 22 h following TH after injection of hyperpolarized 13C-1 labeled pyruvate. The dynamic HP-13C MRSIs were acquired to examine the cerebral metabolic profile, i.e., the conversion rate from pyruvate to lactate (kPL) and the ratio of lactate to pyruvate (Lac/Pyr) in the injured hemisphere. T2-weighted images (T2WI) and diffusion MR images (dMRIs) were acquired to identify the anatomical structures and assess the injury. Mice brains were collected during and at 0 h, 4 h, 12 h, 18 h and 22 h after treatments for western blot to investigate the time course of the levels of the cold stress protein (RNA binding motif 3, RBM3) and cell death markers (spectrin 145/150 and spectrin 120) changes. The cerebral metabolic profile, RBM3 and spectrin levels, and injury size were compared across groups and between specific timepoints. The relationship between the cerebral metabolic profile and RBM3 levels in HI+TH group was also evaluated.Results: We observed the upregulation of RBM3 during TH at 4 h and 22 h after TH. The spectrin 145/150 and spectrin 120 were unchanged over time in HI+TH group, whereas they significantly increased at 18 h and 22 h in HI+NT group. Additionally, the injury size was noticeably larger at 22 h in HI+NT group. Lower kPL and Lac/Pyr were observed at 4 h and 22 h after TH, with a negative correlation to RBM3 levels in HI+TH group.Conclusion: This study demonstrates that RBM3 may be one of the key factors associated with TH-induced neuroprotection by reducing the anaerobic glycolysis process in HI mice, suggesting RBM3 upregulation may enhance the efficacy of TH for neonatal HIE.","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-22"},"PeriodicalIF":2.0000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000548626","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: The efficacy of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) is inconsistent, and the cause remains unclear. This study aimed to explore the role of cold stress protein in the TH-induced neuroprotection following hypoxia-ischemia (HI) using metabolic MRI.

Methods: Postnatal day 10 (P10) mice underwent unilateral HI followed by treatments with therapeutic hypothermia (TH) or normothermia (NT). HI and sham mice were scanned at 4 h and 22 h following TH after injection of hyperpolarized 13C-1 labeled pyruvate. The dynamic HP-13C MRSIs were acquired to examine the cerebral metabolic profile, i.e., the conversion rate from pyruvate to lactate (kPL) and the ratio of lactate to pyruvate (Lac/Pyr) in the injured hemisphere. T2-weighted images (T2WI) and diffusion MR images (dMRIs) were acquired to identify the anatomical structures and assess the injury. Mice brains were collected during and at 0 h, 4 h, 12 h, 18 h and 22 h after treatments for western blot to investigate the time course of the levels of the cold stress protein (RNA binding motif 3, RBM3) and cell death markers (spectrin 145/150 and spectrin 120) changes. The cerebral metabolic profile, RBM3 and spectrin levels, and injury size were compared across groups and between specific timepoints. The relationship between the cerebral metabolic profile and RBM3 levels in HI+TH group was also evaluated.

Results: We observed the upregulation of RBM3 during TH at 4 h and 22 h after TH. The spectrin 145/150 and spectrin 120 were unchanged over time in HI+TH group, whereas they significantly increased at 18 h and 22 h in HI+NT group. Additionally, the injury size was noticeably larger at 22 h in HI+NT group. Lower kPL and Lac/Pyr were observed at 4 h and 22 h after TH, with a negative correlation to RBM3 levels in HI+TH group.

Conclusion: This study demonstrates that RBM3 may be one of the key factors associated with TH-induced neuroprotection by reducing the anaerobic glycolysis process in HI mice, suggesting RBM3 upregulation may enhance the efficacy of TH for neonatal HIE.

查看原文本刊更多论文

代谢MRI检测小鼠缺氧缺血模型冷诱导RNA结合基序3与低温效应的关系

导读：治疗性低温（TH）治疗新生儿缺氧缺血性脑病（HIE）的疗效不一致，原因尚不清楚。本研究旨在利用代谢MRI探讨冷应激蛋白在th诱导的缺氧缺血（HI）后神经保护中的作用。方法：出生后第10天（P10）小鼠进行单侧HI治疗，然后进行治疗性低温（TH）或正常体温（NT）治疗。注射超极化13C-1标记丙酮酸后，分别于TH后4 h和22 h对HI和sham小鼠进行扫描。通过动态HP-13C核磁共振成像检测脑代谢谱，即损伤半球丙酮酸到乳酸的转化率（kPL）和乳酸与丙酮酸的比值（Lac/Pyr）。通过t2加权图像（T2WI）和弥散MR图像（dmri）来识别解剖结构和评估损伤。在处理后0 h、4 h、12 h、18 h和22 h采集小鼠脑，进行western blot检测冷应激蛋白（RNA结合基序3，RBM3）和细胞死亡标志物（spectrin 145/150和spectrin 120）水平变化的时间过程。脑代谢谱、RBM3和spectrin水平以及损伤大小在组间和特定时间点之间进行比较。同时评估HI+TH组脑代谢谱与RBM3水平的关系。结果：我们观察到RBM3在TH期间（TH后4 h和22 h）表达上调。HI+TH组spectrin 145/150和spectrin 120随时间变化不变，而HI+NT组在18 h和22 h时显著升高。此外，HI+NT组在22 h时损伤大小明显更大。HI+TH组在TH后4 h和22 h kPL和Lac/Pyr均较低，且与RBM3水平呈负相关。结论：本研究表明RBM3可能是TH诱导的HI小鼠无氧糖酵解过程中神经保护的关键因素之一，提示RBM3上调可增强TH治疗新生儿HIE的疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Developmental Neuroscience 医学-发育生物学

CiteScore

4.00

自引率

3.40%

发文量

审稿时长

>12 weeks

期刊介绍： ''Developmental Neuroscience'' is a multidisciplinary journal publishing papers covering all stages of invertebrate, vertebrate and human brain development. Emphasis is placed on publishing fundamental as well as translational studies that contribute to our understanding of mechanisms of normal development as well as genetic and environmental causes of abnormal brain development. The journal thus provides valuable information for both physicians and biologists. To meet the rapidly expanding information needs of its readers, the journal combines original papers that report on progress and advances in developmental neuroscience with concise mini-reviews that provide a timely overview of key topics, new insights and ongoing controversies. The editorial standards of ''Developmental Neuroscience'' are high. We are committed to publishing only high quality, complete papers that make significant contributions to the field.