{"title":"缺血性中风和出血性脑损伤中脂质结合素-2的机制研究:整合动物和临床研究。","authors":"Korsin Laohavisudhi , Sirawit Sriwichaiin , Tanawat Attachaipanich , Borwon Wittayachamnankul , Nipon Chattipakorn , Siriporn Chattipakorn","doi":"10.1016/j.expneurol.2024.114885","DOIUrl":null,"url":null,"abstract":"<div><p>Brain injuries, including strokes and traumatic brain injuries (TBI), are a major global health concern, contributing significantly to both mortality and long-term disability. Recent research has identified lipocalin-2 (LCN2), a glycoprotein secreted by various brain cells, as a key factor in influencing brain injury outcomes. Evidence from animal and clinical studies firmly establishes the pivotal role of LCN2 in driving the inflammatory responses triggered by damage to brain tissue. Furthermore, increased LCN2 promotes cellular differentiation, blood-brain barrier breakdown, and decreases cell viability. Interventions with LCN2 inhibitors attenuated brain injury through a reduction in the inflammation process and enhanced cellular viability. Potential mechanisms of LCN2 involve several pathways including the Janus kinase-2 (JAK2)-signal transducers and the transcription-3 (STAT3) signaling, hypoxia-inducible factor 1-alpha (HIF-1α)-LCN2-vascular endothelial growth factor alpha (VEGFα), and the PKR-like ER kinase (PERK) pathways. LCN2 itself interacts with diverse inflammatory cytokines in TBI and intracranial hemorrhage (ICH), resulting in disruption of the blood-brain barrier, increased programmed cell death, and an imbalance in iron homeostasis. Clinical studies have also shown that increased LCN2 level can act as a prognostic biomarker of outcomes following brain injuries. Therefore, this review aims to comprehensively evaluate the role and underlying mechanisms of LCN2 in brain injuries, including stroke and TBI, and explore potential therapeutic interventions targeting LCN2 in these conditions.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanistic insights into Lipocalin-2 in ischemic stroke and hemorrhagic brain injury: Integrating animal and clinical studies\",\"authors\":\"Korsin Laohavisudhi , Sirawit Sriwichaiin , Tanawat Attachaipanich , Borwon Wittayachamnankul , Nipon Chattipakorn , Siriporn Chattipakorn\",\"doi\":\"10.1016/j.expneurol.2024.114885\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Brain injuries, including strokes and traumatic brain injuries (TBI), are a major global health concern, contributing significantly to both mortality and long-term disability. Recent research has identified lipocalin-2 (LCN2), a glycoprotein secreted by various brain cells, as a key factor in influencing brain injury outcomes. Evidence from animal and clinical studies firmly establishes the pivotal role of LCN2 in driving the inflammatory responses triggered by damage to brain tissue. Furthermore, increased LCN2 promotes cellular differentiation, blood-brain barrier breakdown, and decreases cell viability. Interventions with LCN2 inhibitors attenuated brain injury through a reduction in the inflammation process and enhanced cellular viability. Potential mechanisms of LCN2 involve several pathways including the Janus kinase-2 (JAK2)-signal transducers and the transcription-3 (STAT3) signaling, hypoxia-inducible factor 1-alpha (HIF-1α)-LCN2-vascular endothelial growth factor alpha (VEGFα), and the PKR-like ER kinase (PERK) pathways. LCN2 itself interacts with diverse inflammatory cytokines in TBI and intracranial hemorrhage (ICH), resulting in disruption of the blood-brain barrier, increased programmed cell death, and an imbalance in iron homeostasis. Clinical studies have also shown that increased LCN2 level can act as a prognostic biomarker of outcomes following brain injuries. Therefore, this review aims to comprehensively evaluate the role and underlying mechanisms of LCN2 in brain injuries, including stroke and TBI, and explore potential therapeutic interventions targeting LCN2 in these conditions.</p></div>\",\"PeriodicalId\":12246,\"journal\":{\"name\":\"Experimental Neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014488624002115\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014488624002115","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
脑损伤,包括脑卒中和创伤性脑损伤(TBI),是全球关注的主要健康问题,是导致死亡和长期残疾的重要因素。最新研究发现,脂钙蛋白-2(LCN2)是由各种脑细胞分泌的一种糖蛋白,是影响脑损伤结果的关键因素。来自动物和临床研究的证据牢固确立了 LCN2 在推动脑组织损伤引发的炎症反应中的关键作用。此外,LCN2 的增加会促进细胞分化、破坏血脑屏障并降低细胞活力。使用 LCN2 抑制剂进行干预可通过减少炎症过程和提高细胞活力来减轻脑损伤。LCN2 的潜在机制涉及多个途径,包括 Janus 激酶-2(JAK2)-信号转导和转录-3(STAT3)信号、缺氧诱导因子 1-α(HIF-1α)-LCN2-血管内皮生长因子α(VEGFα)和 PKR 样 ER 激酶(PERK)途径。在创伤性脑损伤和颅内出血(ICH)中,LCN2 本身与多种炎症细胞因子相互作用,导致血脑屏障破坏、程序性细胞死亡增加以及铁平衡失调。临床研究还表明,LCN2 水平的升高可作为脑损伤后预后的生物标志物。因此,本综述旨在全面评估 LCN2 在脑损伤(包括中风和创伤性脑损伤)中的作用和潜在机制,并探讨针对 LCN2 的潜在治疗干预措施。
Mechanistic insights into Lipocalin-2 in ischemic stroke and hemorrhagic brain injury: Integrating animal and clinical studies
Brain injuries, including strokes and traumatic brain injuries (TBI), are a major global health concern, contributing significantly to both mortality and long-term disability. Recent research has identified lipocalin-2 (LCN2), a glycoprotein secreted by various brain cells, as a key factor in influencing brain injury outcomes. Evidence from animal and clinical studies firmly establishes the pivotal role of LCN2 in driving the inflammatory responses triggered by damage to brain tissue. Furthermore, increased LCN2 promotes cellular differentiation, blood-brain barrier breakdown, and decreases cell viability. Interventions with LCN2 inhibitors attenuated brain injury through a reduction in the inflammation process and enhanced cellular viability. Potential mechanisms of LCN2 involve several pathways including the Janus kinase-2 (JAK2)-signal transducers and the transcription-3 (STAT3) signaling, hypoxia-inducible factor 1-alpha (HIF-1α)-LCN2-vascular endothelial growth factor alpha (VEGFα), and the PKR-like ER kinase (PERK) pathways. LCN2 itself interacts with diverse inflammatory cytokines in TBI and intracranial hemorrhage (ICH), resulting in disruption of the blood-brain barrier, increased programmed cell death, and an imbalance in iron homeostasis. Clinical studies have also shown that increased LCN2 level can act as a prognostic biomarker of outcomes following brain injuries. Therefore, this review aims to comprehensively evaluate the role and underlying mechanisms of LCN2 in brain injuries, including stroke and TBI, and explore potential therapeutic interventions targeting LCN2 in these conditions.
期刊介绍:
Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.