Stroke-Induced Peripheral Immune Dysfunction in Vitamin D-Deficient Conditions: Modulation by Progesterone and...

Vitamin D deficiency (D^def) alters morphology and outcomes after a stroke. We investigated the interaction of D^def following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. D^def 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^def group compared to the D-sufficient (D^suf) group. Stroke caused peripheral immune dysfunction in the D^suf group which was worse in the D^def group. Systemic inflammation exacerbated injury outcomes in the D^suf group and these were worse in the D^def group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. D^def 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^def.