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Stroke recovery was aided by vitamin D and Progesterone (in rats) – Feb 2019

Stroke Outcomes in Vitamin D-Deficient Conditions: Modulatory Role of Progesterone and Vitamin D

https://doi.org/10.1161/str.50.suppl_1.WP8Stroke. 2019;50:AWP8
Seema Yousuf , Fahim Atif , Claudia Espinosa Garcia , Donald Stein

Introduction: We investigated whether vitamin D (VDH) deficiency is associated with worsened outcomes after stroke with lipopolysaccharide (LPS)-induced inflammation as evaluated by measures of behavioral function, inflammation, endoplasmic reticulum (ER) stress, white matter integrity and peripheral immune response and whether combined progesterone (P) and VDH treatment would improve outcomes under these conditions.

Methods: After 8 weeks on a VDH-deficient diet, adult, male Sprague-Dawley rats underwent transient ischemic stroke (tMCAO). Systemic inflammation was induced 24h post-stroke via 3 doses of LPS (50 μg/kg at 4h intervals). P (8 mg/kg; i.p.) and VDH (1 μg/kg; i.p.) were given 5 min before reperfusion followed by s.c. injections on days 1-7 post-stroke. Groups (n=6) were: Sham VDH-deficient; Sham VDH-sufficient; VDH-deficient tMCAO treated with vehicle; VDH-deficient tMCAO+LPS; VDH-deficient tMCAO+LPS treated with P; VDH-deficient tMCAO+LPS treated with VDH; VDH-deficient tMCAO+LPS treated with P and VDH. At day 7 post-stroke, rats were tested on behavioral parameters, measures of peripheral immune dysfunction, markers of neuronal inflammation (GFAP, Iba-1, IL-6), apoptosis (cleaved caspase-3, TUNEL), ER stress (PERK, eIF2α, CHOP) and white matter integrity (axonal and myelin injury markers SMI-32 and MBP, respectively) in brain. Data were analyzed using ANOVA and the Tukey-HSD post hoc test. Statistical significance was set at P<0.05.

Results: We found significant behavioral deficits in MCAO and MCAO+LPS animals compared to controls. P+VDH significantly improved behavioral outcomes and reduced neuronal inflammation, apoptosis, ER stress and white matter injury compared to the MCAO and MCAO+LPS groups. β cell numbers were significantly reduced in both the MCAO and MCAO+LPS compared to the two sham groups. Peripheral immune dysfunctions revealed by flow cytometric analyses of immune cells in blood, spleen and thymus were significantly restored by combinatorial treatment with P and VDH. P+VDH improved all outcomes significantly more than monotherapy.

Conclusion: The current standard of care for stroke has limited benefit, while combinatorial treatment with P+VDH shows promise for future stroke therapeutics.

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