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基于血液的生物标志物表明,小儿轻度创伤性脑损伤后轴突损伤持续存在。

Blood-based biomarkers suggest prolonged axonal Injury following pediatric mild traumatic brain injury.

作者信息

Mayer Andrew R, Wick Tracey V, McQuaid Jessica R, Boucher Masen L, Dodd Andrew B, Robertson-Benta Cidney R, van der Horn Harm J, Erhardt Erik B, Sapien Robert E, Tarawneh Rawan, Mannix Rebekah

机构信息

The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, 87106, USA.

Departments of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, 87131, USA.

出版信息

Sci Rep. 2025 Feb 4;15(1):4189. doi: 10.1038/s41598-024-84053-4.

DOI:10.1038/s41598-024-84053-4
PMID:39905097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11794578/
Abstract

Pediatric mild traumatic brain injury (pmTBI) affects millions of youth annually but underlying pathophysiology and time for physiological recovery remains unknown. Non-fasting plasma samples were obtained in 59 pmTBI (28 females; age 14.9 ± 2.7) at approximately 7 days and 4 months post-injury and in 41 matched healthy controls (HC: 20 females; age 14.3 ± 2.8). Samples were analyzed for GFAP, NFL, Tau, pTau181 and UCH-L1 protein concentrations in conjunction with a clinical battery. Significant effects of diagnosis (pmTBI > HC) existed at ~ 7 days (p < 0.001; Cohen's d = 0.72) and ~ 4 months (p = 0.015; Cohen's d = 0.41) post-injury for NFL. NFL was also elevated in pmTBI with significant alterations to mental status (e.g., post-traumatic amnesia) relative to patients without (p = 0.014; Cohen's d = 0.77). UCH-L1, GFAP and pTau181 did not differ between groups, but demonstrated negative associations with days post-injury (small to medium effect sizes) suggestive of a more rapid release/clearance. Post-concussive symptoms had the best diagnostic classification accuracy at ~ 7 days, but NFL ranked higher at 4 months post-injury. Preliminary findings highlight dynamic fluctuations in blood-based biomarkers in the first week of pmTBI, with ongoing evidence of protein release (NFL) at 4 months. NFL demonstrated additional promise for delineating injury severity within the spectrum of pmTBI.

摘要

小儿轻度创伤性脑损伤(pmTBI)每年影响数百万青少年,但潜在的病理生理学和生理恢复时间仍不清楚。在59名pmTBI患者(28名女性;年龄14.9±2.7岁)受伤后约7天和4个月时采集非空腹血浆样本,并与41名匹配的健康对照者(HC:20名女性;年龄14.3±2.8岁)进行比较。结合一系列临床检查对样本中的胶质纤维酸性蛋白(GFAP)、神经丝轻链(NFL)、tau蛋白、磷酸化tau蛋白181(pTau181)和泛素羧基末端水解酶L1(UCH-L1)蛋白浓度进行分析。在受伤后约7天(p<0.001;Cohen's d=0.72)和4个月左右(p=0.015;Cohen's d=0.41),NFL存在诊断差异(pmTBI>HC)。与无精神状态改变(如创伤后遗忘)的患者相比,有精神状态显著改变的pmTBI患者NFL水平也升高(p=0.014;Cohen's d=0.77)。UCH-L1、GFAP和pTau181在两组之间无差异,但与受伤后天数呈负相关(效应量小至中等),提示其释放/清除更快。脑震荡后症状在受伤后约7天诊断分类准确性最高,但在受伤后4个月时NFL的诊断价值更高。初步研究结果突出了pmTBI第一周血液生物标志物的动态波动,以及4个月时持续存在的蛋白释放(NFL)证据。NFL在区分pmTBI范围内的损伤严重程度方面显示出更大的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/4dd87cb8cd0f/41598_2024_84053_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/168fb647a7e0/41598_2024_84053_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/3b4023d487ea/41598_2024_84053_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/78af3d564eb7/41598_2024_84053_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/4dd87cb8cd0f/41598_2024_84053_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/168fb647a7e0/41598_2024_84053_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/3b4023d487ea/41598_2024_84053_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/78af3d564eb7/41598_2024_84053_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/11794578/4dd87cb8cd0f/41598_2024_84053_Fig4_HTML.jpg

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