{"title":"脑可塑性和神经炎症蛋白生物标志物与循环 MicroRNAs 作为急性脑损伤预后的预测因子--一项前瞻性队列研究。","authors":"","doi":"10.1016/j.jns.2024.123169","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Brain recovery mechanisms after injuries like aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) involve brain plasticity, synaptic regeneration, and neuroinflammation. We hypothesized that serum levels of the p75 neurotrophic receptor (p75NTR) and associated signaling proteins, as well as differentially expressed (DE) microRNAs, could predict recovery outcomes irrespective of injury type.</p></div><div><h3>Methods</h3><p>A prospective patient cohort with ischemic stroke (IS, <em>n</em> = 30), aneurysmal subarachnoid hemorrhage (aSAH, <em>n</em> = 31), and traumatic brain injury (TBI, <em>n</em> = 13) were evaluated (total <em>n</em> = 74). Serum samples were collected at two post-injury intervals (early: 1–3 days, late: 4–8 days), and outcomes were assessed after three months using the modified Rankin Scale (mRS), categorizing outcomes as favorable (mRS 0–3) or unfavorable (mRS 4–6). Six proteins were measured using ELISAs: p75NTR, NGF, sortilin, IL1β, TNFα, and cyclophilin. DE microRNAs were identified using DESeq2, and their target genes were predicted. Serum molecules between patients with differing outcomes were compared using a Kolmogorov-Smirnov test, 2-tailed <em>t</em>-test and multivariate linear discriminant analysis (LDA).</p></div><div><h3>Results</h3><p>Favorable (<em>n</em> = 46) and unfavorable (<em>n</em> = 28) outcome cohorts were balanced with age and sex (<em>p</em> = 0.25 and 0.63). None of the studied proteins correlated with age. Combinatory LDA of the six protein biomarkers indicated strong prognostic value for favorable outcomes (OR 2.09; AUC = 70.3%, <em>p</em> = 0.0058). MicroRNA expression changes over time were identified in the aSAH, TBI, and IS groups (<em>p</em> < 0.05, FDR corrected). Twenty-three microRNAs were commonly DE across all brain injury groups when comparing favorable and unfavorable outcomes (p < 0.05). LDA of four microRNAs targeting the studied proteins showed high prognostic accuracy (OR 11.7; AUC = 94.1%, <em>p</em> = 0.016).</p></div><div><h3>Conclusions</h3><p>The combined prognostic microRNA and protein biomarker models demonstrated accurate outcome prognostication across diverse injury types, implying the presence of a common recovery mechanism. DE microRNAs were found to target the studied molecules, suggesting a potential mechanistic role in recovery. Further investigation is warranted to study these molecules in prognostication, as well as therapeutic targets for enhancing recovery.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022510X24003046/pdfft?md5=82beeb5d38ee741fe99b38cda9b93b8a&pid=1-s2.0-S0022510X24003046-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Brain plasticity and neuroinflammatory protein biomarkers with circulating MicroRNAs as predictors of acute brain injury outcome – A prospective cohort study\",\"authors\":\"\",\"doi\":\"10.1016/j.jns.2024.123169\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Brain recovery mechanisms after injuries like aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) involve brain plasticity, synaptic regeneration, and neuroinflammation. We hypothesized that serum levels of the p75 neurotrophic receptor (p75NTR) and associated signaling proteins, as well as differentially expressed (DE) microRNAs, could predict recovery outcomes irrespective of injury type.</p></div><div><h3>Methods</h3><p>A prospective patient cohort with ischemic stroke (IS, <em>n</em> = 30), aneurysmal subarachnoid hemorrhage (aSAH, <em>n</em> = 31), and traumatic brain injury (TBI, <em>n</em> = 13) were evaluated (total <em>n</em> = 74). Serum samples were collected at two post-injury intervals (early: 1–3 days, late: 4–8 days), and outcomes were assessed after three months using the modified Rankin Scale (mRS), categorizing outcomes as favorable (mRS 0–3) or unfavorable (mRS 4–6). Six proteins were measured using ELISAs: p75NTR, NGF, sortilin, IL1β, TNFα, and cyclophilin. DE microRNAs were identified using DESeq2, and their target genes were predicted. Serum molecules between patients with differing outcomes were compared using a Kolmogorov-Smirnov test, 2-tailed <em>t</em>-test and multivariate linear discriminant analysis (LDA).</p></div><div><h3>Results</h3><p>Favorable (<em>n</em> = 46) and unfavorable (<em>n</em> = 28) outcome cohorts were balanced with age and sex (<em>p</em> = 0.25 and 0.63). None of the studied proteins correlated with age. Combinatory LDA of the six protein biomarkers indicated strong prognostic value for favorable outcomes (OR 2.09; AUC = 70.3%, <em>p</em> = 0.0058). MicroRNA expression changes over time were identified in the aSAH, TBI, and IS groups (<em>p</em> < 0.05, FDR corrected). Twenty-three microRNAs were commonly DE across all brain injury groups when comparing favorable and unfavorable outcomes (p < 0.05). LDA of four microRNAs targeting the studied proteins showed high prognostic accuracy (OR 11.7; AUC = 94.1%, <em>p</em> = 0.016).</p></div><div><h3>Conclusions</h3><p>The combined prognostic microRNA and protein biomarker models demonstrated accurate outcome prognostication across diverse injury types, implying the presence of a common recovery mechanism. DE microRNAs were found to target the studied molecules, suggesting a potential mechanistic role in recovery. Further investigation is warranted to study these molecules in prognostication, as well as therapeutic targets for enhancing recovery.</p></div>\",\"PeriodicalId\":17417,\"journal\":{\"name\":\"Journal of the Neurological Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-08-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0022510X24003046/pdfft?md5=82beeb5d38ee741fe99b38cda9b93b8a&pid=1-s2.0-S0022510X24003046-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Neurological Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022510X24003046\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Neurological Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022510X24003046","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Brain plasticity and neuroinflammatory protein biomarkers with circulating MicroRNAs as predictors of acute brain injury outcome – A prospective cohort study
Background
Brain recovery mechanisms after injuries like aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) involve brain plasticity, synaptic regeneration, and neuroinflammation. We hypothesized that serum levels of the p75 neurotrophic receptor (p75NTR) and associated signaling proteins, as well as differentially expressed (DE) microRNAs, could predict recovery outcomes irrespective of injury type.
Methods
A prospective patient cohort with ischemic stroke (IS, n = 30), aneurysmal subarachnoid hemorrhage (aSAH, n = 31), and traumatic brain injury (TBI, n = 13) were evaluated (total n = 74). Serum samples were collected at two post-injury intervals (early: 1–3 days, late: 4–8 days), and outcomes were assessed after three months using the modified Rankin Scale (mRS), categorizing outcomes as favorable (mRS 0–3) or unfavorable (mRS 4–6). Six proteins were measured using ELISAs: p75NTR, NGF, sortilin, IL1β, TNFα, and cyclophilin. DE microRNAs were identified using DESeq2, and their target genes were predicted. Serum molecules between patients with differing outcomes were compared using a Kolmogorov-Smirnov test, 2-tailed t-test and multivariate linear discriminant analysis (LDA).
Results
Favorable (n = 46) and unfavorable (n = 28) outcome cohorts were balanced with age and sex (p = 0.25 and 0.63). None of the studied proteins correlated with age. Combinatory LDA of the six protein biomarkers indicated strong prognostic value for favorable outcomes (OR 2.09; AUC = 70.3%, p = 0.0058). MicroRNA expression changes over time were identified in the aSAH, TBI, and IS groups (p < 0.05, FDR corrected). Twenty-three microRNAs were commonly DE across all brain injury groups when comparing favorable and unfavorable outcomes (p < 0.05). LDA of four microRNAs targeting the studied proteins showed high prognostic accuracy (OR 11.7; AUC = 94.1%, p = 0.016).
Conclusions
The combined prognostic microRNA and protein biomarker models demonstrated accurate outcome prognostication across diverse injury types, implying the presence of a common recovery mechanism. DE microRNAs were found to target the studied molecules, suggesting a potential mechanistic role in recovery. Further investigation is warranted to study these molecules in prognostication, as well as therapeutic targets for enhancing recovery.
期刊介绍:
The Journal of the Neurological Sciences provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world. JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials).
JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials. Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world. Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.