The Role of Mineralocorticoid Receptor Expression in Brain Remodeling after Cerebral Ischemia

Abstract

Mineralocorticoid receptors (MRs) are classically known to be expressed in the distal collecting duct of the kidney. Recently it was reported that MR is identified in the heart and vasculature. Although MR expression is also found in the brain, it is restricted to the hippocampus and cerebral cortex under normal condition, and the role played by MRs in brain remodeling after cerebral ischemia remains unclear. In the present study, we used the mouse 20-min middle cerebral artery occlusion model to examine the time course of MR expression and activity in the ischemic brain. We found that MR-positive cells remarkably increased in the ischemic striatum, in which MR expression is not observed under normal conditions, during the acute and, especially, subacute phases after stroke and that the majority of MR-expressing cells were astrocytes that migrated to the ischemic core. Treatment with the MR antagonist spironolactone markedly suppressed superoxide production within the infarct area during this period. Quantitative real-time RT-PCR revealed that spironolactone stimulated the expression of neuroprotective or angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), whereas immunohistochemical analysis showed astrocytes to be cells expressing bFGF and VEGF. Thereby the incidence of apoptosis was reduced. The up-regulated bFGF and VEGF expression also appeared to promote endogenous angiogenesis and blood flow within the infarct area and to increase the number of neuroblasts migrating toward the ischemic striatum. By these beneficial effects, the infarct volume was significantly reduced in spironolactone-treated mice. Spironolactone may thus provide therapeutic neuroprotective effects in the ischemic brain after stroke.

Saha Suppresses Peritoneal Fibrosis in Mice

“…The following antibodies were used for immunofluorescence staining: (1) rabbit anti-human acetylhistone H3 (Lys9) antibody, diluted 1:100 (#9671; Cell HDACI FOR PERITONEAL FIBROSIS (28); BMP-7, 5′-CACTCCCTCCTCAACCCTCGGCA-3′ (forward) and 5′-TAGAGGCATCATAGGCCAGGTGCCC-3′ ( re ve r s e ) ( 2 9 ) ; α 1 c h a i n o f t y p e I c o l l agen (COLIα1), 5′-TGGTCCTGCCGGTCCTCCTG-3′ (forward) and 5′-ACACATTGGGGGTAGGAACA-3′ (reverse) (30); Fibronectin, 5′-GAAACGGCCAACTCCGTCAC-3′ (for w ard) and 5′ -TGGGG TGCC AG TGG TCTCTT-3′ (reverse) (31); Connective tissue growth factor (CTGF), 5′-TGCCAGAACGCACACTGAGG-3′ (forward) and 5′-ATTGCCCTCCCCGGTTACAC-3′ (reverse) (31).…”

Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

“…14,15 The AT 1 receptor and MR have been clearly identified in numerous specific regions in the brain and spinal cord. 16,17 Moreover, it has been suggested the AT 1 receptor and MR are expressed in cultured astrocytes and neurons 18,19 and mediate Ang II-induced astrocyte proliferation. 18 Numerous studies indicate that Ang II and Aldo are key stimulators of oxidative stress, which can trigger multiple signaling mechanisms in the CNS and in the cardiovascular system.…”

NADPH oxidase-mediated Rac1 GTP activity is necessary for nongenomic actions of the mineralocorticoid receptor in the CA1 region of the rat hippocampus

“…Thus, MRs and GRs can cope with stress by coordinating memory formation through both nongenomic and genomic actions. Furthermore, it has recently been reported that cerebral ischemia induces MR expression and ROS production in the cortex and that MR blockers reduce ROS accumulation (32). MR expression has also been found to govern the fate of neurons in ischemic areas (23).…”