Exogenous NADPH could mitigate pyroptosis-induced brain injury in fetal mice exposed to gestational intermittent hypoxia

• Published in: International immunopharmacology 2024-06, Vol.135, p.112311, Article 112311
• Main Authors: Wei, Jiayun, Zheng, Weikun, Teng, Chenjiong, An, Xueqian, Li, Lingling, Zhong, Peipei, Peng, Chenlei, Zhuge, Shurui, Akoto Ampadu, Janet, Yu, Chenyi, Cai, Xiaohong
• Format: Article
• Language: English
• Subjects: Cognitive dysfunction; Exogenous NADPH; Gestational intermittent hypoxia; Obstructive sleep apnea during pregnancy; Pyroptosis
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112311

•This study explores the potential role of exogenous NADPH in mitigating pyroptosis-induced brain injury in fetal mice.•A novel mechanistic insight into brain developmental damage induced by intermittent hypoxia during pregnancy is provided.•Our findings propose a potential intervention strategy, using exogenous NADPH, to alleviate brain damage in fetal mice exposed to hypoxia.•This research offers substantial guidance for future clinical interventions in cases of fetal brain injuries resulting from maternal obstructive sleep apnea.•Our in-depth exploration contributes to the understanding of the biochemical basis of hypoxia-related brain damage, leading to new therapeutic approaches. Obstructive Sleep Apnea (OSA) during pregnancy is characterized by intermittent hypoxia (IH) during sleep and will lead to the rise of oxidative stress in the fetal body. Pyroptosis, a type of inflammatory and programmable cell death mediated by Gasdermin D (GSDMD), plays a substantial role in oxygen deprivation’s contribution to neural system damage. Existing research shows that Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a protective role in alleviating brain tissue pyroptosis. We speculate that exogenous NADPH may play a protective role in OSA during pregnancy. A model of GIH group was established to simulate the pathophysiological mechanisms of OSA during pregnant and AIR group was established by giving the same frequency. Sham group was established by injecting NS and the NADPH group was established and given exogenous NADPH. We utilized the Morris Water Maze to assess cognitive function impairment, Luxol Fast Blue (LBF) staining to confirm myelin sheath formation, TUNEL staining to examine cell death in fetal mice brain tissue, and Western blotting to detect pertinent protein expressions. The GIH group offspring exhibited decreases in spatial learning and memory abilities, reduced numbers of oligodendrocytes and formed myelin, as well as increased expression of pyroptosis-related proteins. The NADPH group offspring showed restoration in spatial learning and memory abilities increased counts of oligodendrocytes and formed myelin sheaths, in addition to decreased expression of pyroptosis-related. This study demonstrates that early injection of exogenous NADPH can alleviate the damage to fetal brain development caused by gestational intermittent hypoxia (GIH).