持续炎症在围产期脑损伤后恢复失败中的作用：解决是治愈吗？
The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?
摘要(中文译文)
围产期脑损伤（PBI）是神经发育残疾的重要预测因素。PBI通常与早产、感染、卒中、缺氧缺血、出血和/或毒素暴露相关，可触发急性和持续性的全身炎症反应。发育过程中存在多个对PBI的易感阶段，包括妊娠期、足月与早产分娩期以及新生儿期。这些易感阶段可通过损伤胎盘-胎儿-脑轴、适应性免疫与固有免疫系统发育、神经-免疫通讯以及中枢神经系统成熟等途径加剧炎症。新生儿对不同病因表现出独特的炎症特征和持久的神经免疫应答。慢性免疫失调以及对继发性、生命后期免疫挑战的预致敏定义了不同形式的PBI，同时通过长期变化塑造新生儿和成人免疫应答。免疫调节性改变影响调节性T细胞、辅助性T细胞和固有T细胞、中性粒细胞、自然杀伤细胞及免疫反应性。PBI中持续性和叠加性炎症的主要途径包括围产期神经-免疫相互作用、细胞因子涌入以及胶质细胞间交互对话。大多数治疗措施的给药时间不够长或未处于最佳时间窗口，无法对抗PBI病理生理学第三和第四阶段中的持续性炎症，且在降低新生儿死亡率和发病率及促进功能恢复方面效果不佳。事实上，持续性的全身和中枢炎症可能是急性损伤消退后PBI恢复失败的原因。我们提出，减轻持续性炎症并使全身免疫反应性正常化是通过多种途径（包括治疗性干预、肠道微生物组调节以及来自临床前研究的新型免疫调节）减少PBI全生命周期功能影响的关键。
Abstract
Perinatal brain injury (PBI) is a major predictor of neurological disability. Commonly associated with prematurity, infection, stroke, hypoxia-ischemia, hemorrhage, and/or toxin exposure, PBI triggers acute and persistent systemic inflammation. There are many stages of vulnerability to PBI during development including pregnancy, birth - term and preterm, and neonatal age. The vulnerable stages can compound inflammation through injury to the placental-fetal-brain axis, adaptive and innate immune system development, neural-immune communication, and central nervous system maturation. Neonates exhibit unique inflammatory signatures and lasting neural-immune responses to various etiologies. Chronic immune dysregulation and priming to a secondary, later-in-life immune challenge defines different forms of PBI while shaping the neonatal and adult immune response with long-term changes. Immunomodulated changes impact regulatory, helper and innate T cells, neutrophils, natural killer cells and immune responsiveness. The major routes of persistent and compounding inflammation in PBI are perinatal neural-immune interactions, cytokine influx, and glial crosstalk. Most treatments are not administered long enough or in the optimal time window to combat sustained inflammation in tertiary and quaternary phases of PBI pathophysiology and are ineffective in reducing neonatal mortality and morbidity and promoting functional recovery. Indeed, persistent systemic and central inflammation is a likely explanation for failed recovery of PBI after the resolution of acute insults. We propose attenuating persistent inflammation and normalizing systemic immune reactivity as key to reducing the functional impact of PBI throughout the lifespan through various avenues including therapeutic treatment, gut microbiome modulation, and novel immunomodulation from preclinical research.
如何引用
AMA
Hawley Helmbrecht, Maryam Ardalan, Lynne Kelly, Shenandoah Robinson, Bobbi Fleiss, Derek G Doherty, et al. The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?. Journal of neuroinflammation. 2026; doi:10.1186/s12974-026-03900-5.
APA
Hawley Helmbrecht, Maryam Ardalan, Lynne Kelly, Shenandoah Robinson, Bobbi Fleiss, Derek G Doherty, et al (2026). The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?. Journal of neuroinflammation. https://doi.org/10.1186/s12974-026-03900-5
GB/T 7714
Hawley Helmbrecht, Maryam Ardalan, Lynne Kelly, Shenandoah Robinson, Bobbi Fleiss, Derek G Doherty, et al. The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?[J]. Journal of neuroinflammation, 2026 doi:10.1186/s12974-026-03900-5.
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