Huang Taida, Huang Xiaomin, Li Hui, Qi Junhua, Wang Nan, Xu Yi, Zeng Yunxin, Xiao Xuewen, Liu Ruide, Chan Yik Lung, Oliver Brian G, Yi Chenju, Li Dan, Chen Hui
Department of Pathology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Front Cell Neurosci. 2022 Feb 18;16:818536. doi: 10.3389/fncel.2022.818536. eCollection 2022.
Hypoxic-ischemic encephalopathy affects ∼6 in 1,000 preterm neonates, leading to significant neurological sequela (e.g., cognitive deficits and cerebral palsy). Maternal smoke exposure (SE) is one of the common causes of neurological disorders; however, female offspring seems to be less affected than males in our previous study. We also showed that maternal SE exaggerated neurological disorders caused by neonatal hypoxic-ischemic brain injury in adolescent male offspring. Here, we aimed to examine whether female littermates of these males are protected from such insult.
BALB/c dams were exposed to cigarette smoke generated from 2 cigarettes twice daily for 6 weeks before mating, during gestation and lactation. To induce hypoxic-ischemic brain injury, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen) at postnatal day (P) 10. Behavioral tests were performed at P40-44, and brain tissues were collected at P45.
Maternal SE worsened the defects in short-term memory and motor function in females with hypoxic-ischemic injury; however, reduced anxiety due to injury was observed in the control offspring, but not the SE offspring. Both hypoxic-ischemic injury and maternal SE caused significant loss of neuronal cells and synaptic proteins, along with increased oxidative stress and inflammatory responses.
Oxidative stress and inflammatory response due to maternal SE may be the mechanism of worsened neurological outcomes by hypoxic-ischemic brain injury in females, which was similar to their male littermates shown in our previous study.
缺氧缺血性脑病影响约千分之六的早产新生儿，导致严重的神经后遗症（如认知缺陷和脑瘫）。母亲吸烟暴露（SE）是神经障碍的常见原因之一；然而，在我们之前的研究中，雌性后代似乎比雄性受影响更小。我们还表明，母亲吸烟暴露会加剧青春期雄性后代因新生儿缺氧缺血性脑损伤引起的神经障碍。在此，我们旨在研究这些雄性的雌性同窝仔是否能免受此类损伤。
BALB/c母鼠在交配前、妊娠期和哺乳期每天两次暴露于两支香烟产生的烟雾中，持续6周。为诱导缺氧缺血性脑损伤，每窝一半的幼崽进行左颈动脉结扎，然后在出生后第10天暴露于8%氧气（92%氮气）环境中。在出生后第40 - 44天进行行为测试，并在出生后第45天收集脑组织。
母亲吸烟暴露使患有缺氧缺血性损伤的雌性的短期记忆和运动功能缺陷恶化；然而，在对照后代中观察到因损伤导致的焦虑减轻，而在吸烟暴露后代中未观察到。缺氧缺血性损伤和母亲吸烟暴露均导致神经元细胞和突触蛋白显著丢失，同时氧化应激和炎症反应增加。
母亲吸烟暴露引起的氧化应激和炎症反应可能是雌性因缺氧缺血性脑损伤导致神经结局恶化的机制，这与我们之前研究中雄性同窝仔的情况相似。
