The Role of Mature Brain-Derived Neurotrophic Factor and Its Precursor in Predicting Early-Onset Insomnia in Stroke Patients Experiencing Early Neurological Deterioration.

IF 3.4 2区医学 Q2 CLINICAL NEUROLOGY Nature and Science of Sleep Pub Date : 2025-02-12 eCollection Date: 2025-01-01 DOI:10.2147/NSS.S500052

Guomei Shi, Peng Yu, Ziru Wang, Mingyang Xu, Minwang Guo, Xiaorong Wang, Rujuan Zhou

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Abstract

Background: The investigation and management of early-onset insomnia (EOI) in patients undergoing early neurological deterioration (END) appear to be insufficiently prioritized in clinical practice. Brain-derived neurotrophic factor (mBDNF) and its precursor, proBDNF, play essential roles in neuroplasticity and may be involved in the pathophysiological mechanisms underlying EOI. This study aimed to investigate the associations of serum mBDNF, proBDNF, and the mBDNF/proBDNF ratio with EOI in stroke patients experiencing END.

Methods: In a prospective cohort study from October 2021 to December 2023, 232 stroke patients with END and 56 healthy controls (HCs) were enrolled. Serum levels of mBDNF and proBDNF were quantified using enzyme-linked immunosorbent assays. EOI was diagnosed according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). Patients with END were categorized into subgroups based on the presence or absence EOI.

Results: Serum levels of mBDNF, proBDNF, and the mBDNF/proBDNF ratio were significantly lower in END patients compared to those in HCs (all p < 0.05). Among the 232 END patients, 82 (35.3%) developed EOI. Those with EOI had significantly lower levels of mBDNF and the mBDNF/proBDNF ratio compared to those without EOI (all p < 0.001). Multivariate logistic regression analysis revealed that male gender (p = 0.026), Hamilton Depression Rating Scale (HAMD) scores (p < 0.001), mBDNF (p = 0.009), and the mBDNF/proBDNF ratio (p < 0.001) were independent predictors of EOI in END patients. The areas under the curve (AUC) for mBDNF and the mBDNF/proBDNF ratio were 0.686 and 0.778, respectively.

Conclusion: Our study identified a correlation between reduced mBDNF levels and a decreased mBDNF/proBDNF ratio with the development of EOI in END patients. In addition, the mBDNF/proBDNF ratio may provide greater insight as a promising biomarker for EOI than mBDNF or proBDNF alone.

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成熟脑源性神经营养因子及其前体在预测早期神经功能恶化的脑卒中患者早发性失眠中的作用。

背景：早期神经功能恶化（END）患者早发性失眠（EOI）的调查和处理在临床实践中似乎没有得到足够的重视。脑源性神经营养因子（mBDNF）及其前体proBDNF在神经可塑性中起着重要作用，并可能参与了EOI的病理生理机制。本研究旨在探讨脑卒中终末期患者血清mBDNF、proBDNF和mBDNF/proBDNF比值与EOI的关系。方法：在2021年10月至2023年12月的一项前瞻性队列研究中，纳入了232例END脑卒中患者和56例健康对照（hc）。采用酶联免疫吸附法测定血清mBDNF和proBDNF水平。根据国际睡眠障碍分类第三版（ICSD-3）诊断为EOI。根据是否存在EOI将END患者分为亚组。结果：END患者血清mBDNF、proBDNF水平及mBDNF/proBDNF比值显著低于hcc患者（均p < 0.05）。232例END患者中，82例（35.3%）发生EOI。EOI患者mBDNF水平和mBDNF/proBDNF比值明显低于无EOI患者（均p < 0.001）。多因素logistic回归分析显示，男性（p = 0.026）、汉密尔顿抑郁评定量表（HAMD）评分（p < 0.001）、mBDNF （p = 0.009）和mBDNF/proBDNF比值（p < 0.001）是END患者EOI的独立预测因子。mBDNF的曲线下面积（AUC）和mBDNF/proBDNF比值分别为0.686和0.778。结论：我们的研究确定了mBDNF水平降低和mBDNF/proBDNF比值降低与END患者EOI的发展之间的相关性。此外，mBDNF/proBDNF比值可能比单独mBDNF或proBDNF更有希望作为EOI的生物标志物。

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来源期刊

Nature and Science of Sleep Neuroscience-Behavioral Neuroscience

CiteScore

5.70

自引率

5.90%

发文量

245

审稿时长

16 weeks

期刊介绍： Nature and Science of Sleep is an international, peer-reviewed, open access journal covering all aspects of sleep science and sleep medicine, including the neurophysiology and functions of sleep, the genetics of sleep, sleep and society, biological rhythms, dreaming, sleep disorders and therapy, and strategies to optimize healthy sleep. Specific topics covered in the journal include: The functions of sleep in humans and other animals Physiological and neurophysiological changes with sleep The genetics of sleep and sleep differences The neurotransmitters, receptors and pathways involved in controlling both sleep and wakefulness Behavioral and pharmacological interventions aimed at improving sleep, and improving wakefulness Sleep changes with development and with age Sleep and reproduction (e.g., changes across the menstrual cycle, with pregnancy and menopause) The science and nature of dreams Sleep disorders Impact of sleep and sleep disorders on health, daytime function and quality of life Sleep problems secondary to clinical disorders Interaction of society with sleep (e.g., consequences of shift work, occupational health, public health) The microbiome and sleep Chronotherapy Impact of circadian rhythms on sleep, physiology, cognition and health Mechanisms controlling circadian rhythms, centrally and peripherally Impact of circadian rhythm disruptions (including night shift work, jet lag and social jet lag) on sleep, physiology, cognition and health Behavioral and pharmacological interventions aimed at reducing adverse effects of circadian-related sleep disruption Assessment of technologies and biomarkers for measuring sleep and/or circadian rhythms Epigenetic markers of sleep or circadian disruption.