Piancone Federica, La Rosa Francesca, Hernis Ambra, Marventano Ivana, Arcuri Pietro, Rabuffetti Marco, Navarro Jorge, Saresella Marina, Clerici Mario, Comanducci Angela
IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy.
Int J Mol Sci. 2025 Sep 4;26(17):8593. doi: 10.3390/ijms26178593.
Traumatic brain injury (TBI), a leading cause of mortality and disability, recognizes a primary, immediate injury due to external forces, and a secondary phase that includes inflammation that can lead to complications such as the post-traumatic confusional state (PTCS), potentially impacting long-term neurological recovery. An earlier identification of these complications, including PTCS, upon admission to intensive rehabilitation units (IRU) could possibly allow the design of personalized rehabilitation protocols in the immediate post-acute phase of moderate-to-severe TBI. The present study aims to identify potential biomarkers to distinguish between TBI patients with and without PTCS. We analyzed cellular and molecular mechanisms involved in neuroinflammation (IL-6, IL-1β, IL-10 cytokines), neuroendocrine function (norepinephrine, NE, epinephrine, E, dopamine), and neurogenesis (glial cell line-derived neurotrophic factor, GDNF, insuline-like growth factor 1, IGF-1, nerve growth factor, NGF, brain-derived growth factor, BDNF) using enzyme-linked immunosorbent assay (ELISA), comparing results between 29 TBI patients (17 with PTCS and 12 non-confused) and 34 healthy controls (HC), and correlating results with an actigraphy-derived sleep efficiency parameter. In TBI patients compared to HC, serum concentration of (1) pro-inflammatory IL-1β cytokine was significantly increased while that of anti-inflammatory IL-10 cytokine was significantly decreased; (2) NE, E and DA were significantly increased; (3) GDNF, NGF and IGF-1 were significantly increased while that of BDNF was significantly decreased. Importantly, IL-10 serum concentration was significantly lower in PTCS than in non-confused patients, correlating positively with an improved actigraphy-derived sleep efficiency parameter. An anti-inflammatory environment may be associated with better prognosis after TBI.
创伤性脑损伤（TBI）是导致死亡和残疾的主要原因，它包括因外力造成的原发性即刻损伤，以及继发性阶段，其中包括炎症，这种炎症可导致诸如创伤后混乱状态（PTCS）等并发症，可能会影响长期神经功能恢复。在入住强化康复单元（IRU）时更早地识别这些并发症，包括PTCS，可能有助于在中重度TBI的急性后期设计个性化康复方案。本研究旨在识别潜在的生物标志物，以区分有和没有PTCS的TBI患者。我们使用酶联免疫吸附测定（ELISA）分析了神经炎症（IL-6、IL-1β、IL-10细胞因子）、神经内分泌功能（去甲肾上腺素、NE、肾上腺素、E、多巴胺）和神经发生（胶质细胞系源性神经营养因子、GDNF、胰岛素样生长因子1、IGF-1、神经生长因子、NGF、脑源性生长因子、BDNF）所涉及的细胞和分子机制，比较了29例TBI患者（17例有PTCS和12例无混乱）和34例健康对照（HC）的结果，并将结果与活动记录仪得出的睡眠效率参数相关联。与HC相比，TBI患者血清中：（1）促炎IL-1β细胞因子浓度显著升高，而抗炎IL-10细胞因子浓度显著降低；（2）NE、E和DA显著升高；（3）GDNF、NGF和IGF-1显著升高，而BDNF显著降低。重要的是，PTCS患者的IL-10血清浓度显著低于无混乱患者，且与活动记录仪得出的睡眠效率参数改善呈正相关。抗炎环境可能与TBI后更好的预后相关。
