Abstract：
Periventricular leukomalacia (PVL) is a neurological condition observed in premature infants, characterized by hypomyelination and activation of microglia. Maternal inflammation-induced brain injury in offspring significantly contributes to the development of PVL. Currently, there are no clinical pharmaceutical interventions available for pregnant women to prevent maternal inflammation-mediated brain injury in their offspring. Inosine has been shown to modulate the immune response in diverse stressful circumstances, such as injury, ischemia, and inflammation. The aim of this investigation was to examine the potential prophylactic impact of inosine on offspring PVL induced by maternal inflammation. This was accomplished by administering a 1 mg/ml inosine solution (40 ml daily) to pregnant Sprague-Dawley (SD) rats for 16 consecutive days prior to their intraperitoneal injection of lipopolysaccharide (350 µg/kg, once a day, for two days). The results showed that maternal inosine pretreatment significantly reversed the reduction in MBP and CNPase (myelin-related markers), CC-1 and Olig2 (oligodendrocyte-related markers) in their PVL pups (P7), suggesting that inosine administration during pregnancy could improve hypomyelination and enhance the differentiation of oligodendrocyte precursor cells (OPCs) in their PVL pups. Furthermore, the protective mechanism of inosine against PVL is closely associated with the activation and polarization of microglia. This is evidenced by a notable reduction in the quantity of IBA 1-positive microglia, a decrease in the level of CD86 (a marker for M1 microglia), an increase in the level of Arg 1 (a marker for M2 microglia), as well as a decrease in the level of pro-inflammatory factors TNF-α, IL-1β, and IL-6, and an increase in the level of anti-inflammatory factors IL-4 and IL-10 in the brain of PVL pups following maternal inosine pretreatment. Taken together, inosine pretreatment of pregnant rats can improve hypomyelination in their PVL offspring by triggering the M1/M2 switch of microglia.
摘要：
脑室周围白质软化（PVL）是在早产儿中观察到的神经系统疾病，以小胶质细胞活化和活化为特征。母体炎症引起的后代脑损伤在PVL的发生中起着重要作用。目前,目前尚无临床药物干预措施可用于孕妇预防母体炎症介导的后代脑损伤.肌苷已被证明在不同的压力环境中调节免疫反应，比如受伤,缺血,和炎症。这项研究的目的是研究肌苷对母体炎症诱导的后代PVL的潜在预防性影响。这是通过在怀孕的Sprague-Dawley（SD）大鼠腹膜内注射脂多糖（350µg/kg，一天一次,两天）。结果表明，母体肌苷预处理显著逆转了MBP和CNPase（髓鞘相关标志物）的降低，CC-1和Olig2（少突胶质细胞相关标志物）在他们的PVL幼崽（P7），这表明在怀孕期间服用肌苷可以改善其PVL幼仔中的低髓鞘形成并增强少突胶质细胞前体细胞（OPCs）的分化。此外，肌苷对PVL的保护机制与小胶质细胞的激活和极化密切相关。IBA1阳性小胶质细胞的数量显着减少证明了这一点，CD86（M1小胶质细胞的标志物）水平降低，Arg1（M2小胶质细胞的标记）水平的增加，以及促炎因子TNF-α水平的降低，IL-1β,母体肌苷预处理后，PVL幼仔脑中抗炎因子IL-4和IL-10水平升高。一起来看,孕鼠肌苷预处理可以通过触发小胶质细胞的M1/M2开关来改善其PVL后代的低磷脂作用。
