Mito

低血糖与认知功能障碍有关，但确切机制尚未阐明。我们之前的研究发现，严重的低血糖可能导致 1 型糖尿病 (T1D) 小鼠模型出现认知功能障碍。因此，本研究旨在进一步探讨严重低血糖导致认知功能障碍的机制是否与氧化应激介导的周细胞丢失和血脑屏障（BBB）渗漏有关。使用雄性 C57BL/6J 小鼠的链脲佐菌素 T1D 模型（150 mg/kg，一次性腹腔注射）用于诱导低血糖。提取脑组织以检查神经元损伤，通过伊文思蓝染色和电子显微镜研究 BBB 的渗透性，测定脑组织中的活性氧和三磷酸腺苷，并确定了周细胞的功能变化。使用 Morris 水迷宫测试认知功能。此外，还构建了体外葡萄糖剥夺模型。结果表明，低血糖后 BBB 渗漏与氧化应激过度激活和葡萄糖剥夺/再灌注引起的线粒体功能障碍有关。在体内和体外模型中使用线粒体靶向抗氧化剂 Mito-TEMPO 进行干预可减少线粒体氧化应激，减少周细胞损失和细胞凋亡，并减轻 BBB 渗漏和神经元损伤，最终改善认知功能。结果表明，低血糖后 BBB 渗漏与氧化应激过度激活和葡萄糖剥夺/再灌注引起的线粒体功能障碍有关。在体内和体外模型中使用线粒体靶向抗氧化剂 Mito-TEMPO 进行干预可减少线粒体氧化应激，减少周细胞损失和细胞凋亡，并减轻 BBB 渗漏和神经元损伤，最终改善认知功能。结果表明，低血糖后 BBB 渗漏与氧化应激过度激活和葡萄糖剥夺/再灌注引起的线粒体功能障碍有关。在体内和体外模型中使用线粒体靶向抗氧化剂 Mito-TEMPO 进行干预可减少线粒体氧化应激，减少周细胞损失和细胞凋亡，并减轻 BBB 渗漏和神经元损伤，最终改善认知功能。

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Hypoglycemia is associated with cognitive dysfunction, but the exact mechanisms have not been elucidated. Our previous study found that severe hypoglycemia could lead to cognitive dysfunction in a type 1 diabetes (T1D) mouse model. Thus, the aim of this study was to further investigate whether the mechanism of severe hypoglycemia leading to cognitive dysfunction is related to oxidative stress-mediated pericyte loss and blood-brain barrier (BBB) leakage. A streptozotocin T1D model (150 mg/kg, one-time intraperitoneal injection), using male C57BL/6J mice, was used to induce hypoglycemia. Brain tissue was extracted to examine for neuronal damage, permeability of BBB was investigated through Evans blue staining and electron microscopy, reactive oxygen species and adenosine triphosphate in brain tissue were assayed, and the functional changes of pericytes were determined. Cognitive function was tested using Morris water maze. Also, an in vitro glucose deprivation model was constructed. The results showed that BBB leakage after hypoglycemia is associated with excessive activation of oxidative stress and mitochondrial dysfunction due to glucose deprivation/reperfusion. Interventions using the mitochondria-targeted antioxidant Mito-TEMPO in both in vivo and in vitro models reduced mitochondrial oxidative stress, decreased pericyte loss and apoptosis, and attenuated BBB leakage and neuronal damage, ultimately leading to improved cognitive function.