Weill Cornell Medicine - New York Presbyterian Hospital, 525 East 68th Street, Suite N-506, New York, NY, 10065, United States.
Weill Cornell Medicine - New York Presbyterian Hospital, 525 East 68th Street, Suite N-506, New York, NY, 10065, United States.
Semin Fetal Neonatal Med. 2020 Aug;25(4):101110. doi: 10.1016/j.siny.2020.101110. Epub 2020 Apr 9.
The fetal inflammatory response syndrome (FIRS) is characterized by umbilical cord inflammation and elevated fetal pro-inflammatory cytokines. Surviving neonates, especially very preterm infants, have increased rates of neonatal morbidity including neurodevelopmental impairment. The mechanism of brain injury in FIRS is complex and may involve "multiple hits." Exposure to in utero inflammation initiates a cascade of the fetal immune response, where pro-inflammatory cytokines can cause direct injury to oligodendrocytes and neurons. Activation of microglia results in further injury to vulnerable pre-myelinating oligodendrocytes and influences the integrity of the fetal and newborn's blood-brain barrier, resulting in further exposure of the brain to developmental insults. Newborns exposed to FIRS are frequently exposed to additional perinatal and postnatal insults that can result in further brain injury. Future directions should include evaluations for new therapeutic interventions aimed at reducing brain injury by dampening FIRS, inhibition of microglial activation, and regeneration of immature oligodendrocytes.
胎儿炎症反应综合征（FIRS）的特征是脐带炎症和胎儿促炎细胞因子升高。存活的新生儿，尤其是极早产儿，其新生儿发病率增加，包括神经发育障碍。FIRS 中脑损伤的机制很复杂，可能涉及“多次打击”。宫内炎症的暴露引发了胎儿免疫反应的级联反应，其中促炎细胞因子可直接损伤少突胶质细胞和神经元。小胶质细胞的激活导致脆弱的未成熟少突胶质细胞进一步受损，并影响胎儿和新生儿血脑屏障的完整性，导致大脑进一步暴露于发育损伤中。暴露于 FIRS 的新生儿经常受到额外的围产期和产后损伤，这可能导致进一步的脑损伤。未来的研究方向应包括评估新的治疗干预措施，通过抑制 FIRS、抑制小胶质细胞激活和不成熟少突胶质细胞的再生来减少脑损伤。
