Ischemic stroke is a cerebrovascular lesion caused by local ischemia and hypoxia. Diabetes mellitus (DM) is a chronic inflammatory disease that disturbs immune homeostasis and predisposes patients to ischemic stroke. The mechanism by which DM exacerbates stroke remains unclear, although it may involve disturbances in immune homeostasis. Regulatory T cells (Tregs) play a regulatory role in many diseases, but the mechanism of Tregs in diabetes complicated by stroke remains unclear. Sodium butyrate is a short-chain fatty acid that increases Treg levels. This study examined the role of sodium butyrate in the prognosis of neurological function in diabetic stroke and the mechanism by which Tregs are amplified in the bilateral cerebral hemispheres. We evaluated the brain infarct volume, observed 48-h neuronal injury and 28-day behavioral changes, and calculated the 28-day survival rate in mice. We also measured Treg levels in peripheral blood and brain tissue, recorded changes in the blood‒brain barrier and water channel proteins and neurotrophic changes in mice, measured cytokine levels and peripheral B-cell distribution in bilateral hemispheres and peripheral blood, and examined the polarization of microglia and the distribution of peripheral T-cell subpopulations in bilateral hemispheres. Diabetes significantly exacerbated the poor prognosis and neurological deficits in mice with stroke, and sodium butyrate significantly improved infarct volume, prognosis, and neurological function and showed different mechanisms in brain tissue and peripheral blood. The potential regulatory mechanism in brain tissue involved modulating Tregs/TGF-β/microglia to suppress neuroinflammation, while that in peripheral blood involved improving the systemic inflammatory response through Tregs/TGF-β/T cells.

Graphical Abstract

中文翻译：

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丁酸钠对糖尿病脑卒中神经元恢复及预后的影响及机制

缺血性中风是局部缺血缺氧引起的脑血管病变。糖尿病 (DM) 是一种慢性炎症性疾病，会扰乱免疫稳态，使患者易患缺血性中风。糖尿病加剧中风的机制仍不清楚，尽管它可能涉及免疫稳态的紊乱。调节性T细胞（Tregs）在多种疾病中发挥调节作用，但Tregs在糖尿病并发脑卒中中的作用机制尚不清楚。丁酸钠是一种短链脂肪酸，可提高 Treg 水平。本研究探讨了丁酸钠在糖尿病卒中神经功能预后中的作用以及 Treg 在双侧大脑半球扩增的机制。我们评估了小鼠的脑梗塞体积，观察了48小时的神经元损伤和28天的行为变化，并计算了小鼠的28天存活率。我们还测量了外周血和脑组织中的Treg水平，记录了小鼠血脑屏障和水通道蛋白的变化以及神经营养学的变化，测量了双侧半球和外周血中的细胞因子水平和外周B细胞分布，并检查了极化小胶质细胞的数量和双侧半球外周 T 细胞亚群的分布。糖尿病显着加剧了中风小鼠的不良预后和神经功能缺损，丁酸钠显着改善了梗死体积、预后和神经功能，并在脑组织和外周血中表现出不同的机制。脑组织中的潜在调节机制涉及调节Tregs/TGF-β/小胶质细胞以抑制神经炎症，而外周血中的潜在调节机制涉及通过Tregs/TGF-β/T细胞改善全身炎症反应。

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