ABSTRACT
INTRODUCTION: Reduction of blood flow below a threshold value in brain regions locally or globally is called cerebral ischemia and proper treatment requires either the restoration of normal blood flow and/or the administration of neuroprotective therapies. Human trophoblast progenitor cells (hTPCs) give rise to the placenta and are responsible for the invasion and vascular remodeling of the maternal vessels within the uterus. Here, we tested whether hTPCs promoted to differentiate along neural lineages may exhibit therapeutic properties in the setting of cerebral ischemia in vivo. MATERIALS AND METHODS: Cerebral ischemia was generated in rats via middle cerebral artery occlusion and, after 24 h, hTPCs were injected systemically via tail vein. Animals were sacrified at Day 3 or 11. RESULTS: TTC staining indicated that infarct volumes were smaller in hTPC treated animals. Visible myelin recovery was observed in the hTPC injected group with Luxol Fast Blue staining. On Day 11 after hTPC transplantation, DLX5 and VEGF expression, as well as 2 and 10 d after hTPC transplantation, NKX2.2 were significantly increased; while LHX6, Olig1, PDGFRα, VEGFR1 and VEGFR2 showed trends toward improved expression in brain tissue via immunoblot analysis. Neuron-like differentiated cells were positive for both NeuN and Cresyl Violet staining. CONCLUSION: Here, we demonstrate for the first time that hTPCs enhance the expression of angiogenic and neurogenic factors in rat brain after stroke. Transplantation of hTPCs could form the basis of novel therapeutic approaches for the treatment of stroke in the clinical setting.
Subject(s)
Brain Ischemia , Stroke , Animals , Brain Ischemia/drug therapy , Female , Humans , Infarction, Middle Cerebral Artery , Neurogenesis , Placenta/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Stem Cells , Stroke/therapy , Trophoblasts/metabolismABSTRACT
Stevia rebaudiana Bertoni, which is a medicinal plant used in the treatment of diabetes, was the focus of this study aiming to investigate its immunomodulatory properties in diabetes. To form the diabetes group, rats were injected intraperitoneally with STZ and rats with blood glucose levels above 200 mg/dL 2 days after STZ injection were included in the diabetes group. To form the stevia and diabetes + stevia groups, stevia was administered daily by gavage to both healthy and diabetic rats for 28 days. At the end of 28 days, the levels of interleukin-1 beta and tumor necrosis factor-alpha in the blood were measured by ELISA. CD3, CD4, and CD8 protein levels in the blood were determined by flow cytometry. Rat body weight increased in the diabetes +25 mg/kg bW stevia group compared with the diabetes group. Blood glucose levels were significantly decreased in the diabetes +25 mg/kg bW stevia group compared to the diabetes group (**p < .01). IL-1ß cytokine levels decreased significantly in the diabetes +25 mg/kg bW stevia group compared to the diabetes group (**p < .01). TNF-α cytokine levels decreased significantly in the diabetes +25 mg/kg bW stevia group compared to the diabetes group (**p < .01). The amount of CD8 + T cells decreased significantly in the diabetes +25 mg/kg bW stevia group compared to the diabetes group (*p < .05). The stevia diet leads to a reduction in peripheral circulating cytotoxic T cells and proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha under hyperglycemic conditions.