Stroke is a leading cause of death and disability, and the available therapies are limited. Stroke stimulates inflammatory mechanisms that exacerbate the damage caused by cerebral ischemia. Interestingly, inflammation is linked to the effects of aldosterone and mineralocorticoid receptor (MR) activation in different organ systems. Previous studies show that chronic MR antagonism before cerebral ischemia improves the outcome of stroke, and MR activation worsens it. The aim of this study was investigate the hypothesis that plasma aldosterone levels increase after cerebral ischemia, and MR antagonists administered post-stroke, will reduce the infarct size by mediating a shift in the phenotype of the immune cells in the brain from pro- to anti-inflammatory. I induced transient focal cerebral ischemia using the middle cerebral artery occlusion technique, and the MR antagonist spironolactone was administered at the time of reperfusion. Plasma aldosterone levels were measured by ELISA, and inflammatory marker expression was analyzed by qRT-PCR. My results indicate that plasma aldosterone levels increase rapidly after the induction of cerebral ischemia in Wistar Kyoto (WKY) rats but not in stroke-prone spontaneously hypertensive rats (SHRSP). MR antagonism post-stroke reduced infarct size in both strains. In SHRSP, but not in WKY rats, MR antagonism increased the expression of anti-inflammatory microglia/macrophages and cytokines, which may be positive for stroke outcome. These results suggest that aldosterone post-stroke exacerbates the injury caused by cerebral ischemia and that MR antagonists are a potential drug for the treatment of stroke.
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