Department of Emergency Medicine, Brain Research Laboratory, Emory University, 615 Michael Street, Room 655A, Atlanta, GA, 30322, USA.
Department of Pharmacology, Emory University, Atlanta, GA, 30322, USA.
Mol Neurobiol. 2021 Mar;58(3):950-963. doi: 10.1007/s12035-020-02129-4. Epub 2020 Oct 16.
Vitamin D deficiency (D) alters morphology and outcomes after a stroke. We investigated the interaction of D following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. D rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were measured along with immune cell populations from the spleen, thymus, and blood. Severely altered outcomes were observed in the D group compared to the D-sufficient (D) group. Stroke caused peripheral immune dysfunction in the D group which was worse in the D group. Systemic inflammation exacerbated injury outcomes in the D group and these were worse in the D group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. D as a comorbid condition with stroke worsens stroke outcomes and can delay functional recovery. Combination treatment with P and D might be promising for future stroke therapeutics in D.
维生素 D 缺乏症（D）会改变中风后的形态和结果。我们研究了中风后全身炎症下 D 的相互作用，并评估了孕激素（P）或维生素 D（D）的给药是否会改善结果。D 型大鼠发生中风，并伴有脂多糖（LPS）诱导的全身炎症。大鼠随机分为 9 组，并接受 P、D 或载体治疗 4 天。在第 4 天，大鼠接受不同行为参数的测试。测量了神经元炎症、内质网应激、氧化应激、白质完整性和细胞凋亡的标志物，以及来自脾脏、胸腺和血液的免疫细胞群体。与 D 充足（D）组相比，D 组的结果严重改变。中风导致 D 组外周免疫功能障碍，而 D 组更严重。全身炎症加重了 D 组的损伤结果，而 D 组更严重。P/D 的单一治疗显示出有益的功能效果，但联合治疗的效果优于单独治疗。D 作为中风的合并症会使中风结果恶化，并可能延迟功能恢复。P 和 D 的联合治疗可能是未来 D 型中风治疗的有希望的方法。
