Xiaodan Liu, Xiangning Jiang, Alkisti Mikrogeorgiou Capper, Nicholas Stewart, Will Byrne, Xiao Ji, Jacob Ellison, Duan Xu, Donna M Ferriero
{"title":"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","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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","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":"{\"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\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"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}","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}
Association between cold-inducible RNA binding motif 3 and hypothermia effect in murine hypoxia-ischemia model measured by metabolic MRI.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
