Brain Research Laboratory, Department of Emergency Medicine, USA.
Brain Research Laboratory, Department of Emergency Medicine, USA.
Neuropharmacology. 2020 Dec 15;181:108327. doi: 10.1016/j.neuropharm.2020.108327. Epub 2020 Sep 18.
Post-stroke systemic inflammation, due to the injury itself and exacerbated by in-hospital infections, can increase morbidity and mortality in stroke patients. In this study, we examined the immunomodulatory effects of progesterone (P4) alone and in combination with vitamin D hormone (VDH) on acute phase post-stroke peripheral immune dysfunction and functional/behavioral deficits. Adult rats underwent transient middle cerebral artery occlusion/reperfusion (tMCAO) and delayed systemic inflammation was induced by injections of lipopolysaccharide (LPS) beginning 24 h post-stroke. Animals were tested for behavioral outcomes and immune function at day 4 post-stroke. We also measured infarction volume and markers of neuronal inflammation (GFAP, IL-6) and apoptosis (cleaved caspase-3) in brain post-stroke. We observed the worst stroke outcomes in the stroke + systemic inflammation group compared to the stroke-alone group. Flow cytometric analysis of different subsets of immune cells in blood, spleen and thymus revealed peripheral immune dysfunction which was restored by both P4 and VDH monotherapy. P4 monotherapy reduced infarction volume, behavioral/functional deficits, peripheral immune dysfunction, neuronal inflammation, and apoptosis induced by post-stroke systemic inflammation. Combination treatment with P4+VDH improved outcomes better than monotherapy. Our findings can be taken to suggest that the current standard of care for stroke and post-stroke infection can be substantially improved by P4 and VDH combination therapy.
中风后的全身炎症，由于损伤本身和医院内感染的加剧，会增加中风患者的发病率和死亡率。在这项研究中，我们研究了单独使用孕激素（P4）和联合使用维生素 D 激素（VDH）对急性中风后外周免疫功能障碍和功能/行为缺陷的免疫调节作用。成年大鼠接受短暂性大脑中动脉闭塞/再灌注（tMCAO），并在中风后 24 小时开始注射脂多糖（LPS）以诱导延迟性全身炎症。在中风后第 4 天对动物进行行为学评估和免疫功能检测。我们还测量了中风后大脑中的梗死体积以及神经元炎症（GFAP、IL-6）和凋亡（cleaved caspase-3）标志物。与单纯中风组相比，中风合并全身炎症组的中风结局最差。对血液、脾脏和胸腺中不同免疫细胞亚群的流式细胞术分析显示，外周免疫功能障碍可通过 P4 和 VDH 单独治疗得到恢复。P4 单独治疗可减轻梗死体积、行为/功能缺陷、外周免疫功能障碍、神经元炎症和由中风后全身炎症引起的凋亡。与单独治疗相比，P4+VDH 的联合治疗改善效果更好。我们的研究结果表明，P4 和 VDH 联合治疗可以显著改善中风和中风后感染的现有治疗标准。
