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Cellular and Molecular Neurobiology

, Volume 39, Issue 4, pp 483–492 | Cite as

Mineralocorticoid Receptors, Neuroinflammation and Hypertensive Encephalopathy

  • Maria Elvira Brocca
  • Luciana Pietranera
  • Edo Ronald de Kloet
  • Alejandro Federico De NicolaEmail author
Review Paper

Abstract

Worldwide, raised blood pressure is estimated to affect 35–40% of the adult population and is a main conditioning factor for cardiovascular diseases and stroke. Animal models of hypertension have provided great advances concerning the pathophysiology of human hypertension, as already shown for the deoxycorticosterone-salt treated rat, the Dahl-salt sensitive rat, the Zucker obese rat and the spontaneously hypertensive rat (SHR). SHR has been widely used to study abnormalities of the brain in chronic hypertension. This review summarises present and past evidence that in the SHR, hypertension causes hippocampal tissue damage which triggers a pro-inflammatory feedforward cascade affecting this vulnerable brain region. The cascade is driven by mineralocorticoid receptor (MR) activation responding to endogenous corticosterone rather than aldosterone. Increased MR expression is a generalised feature of the SHR which seems to support first the rise in blood pressure. Then oxidative stress caused by vasculopathy and hypoxia further increases MR activation in hippocampal neurons and glia cells, activates microglia activation and pro-inflammatory mediators, and down-regulates anti-inflammatory factors. In contrast to MR, involvement of the glucocorticoid receptor (GR) in SHR is less certain. GR showed normal expression levels and blockage with an antagonist failed to reduce blood pressure of SHR. The findings support the concept that MR:GR imbalance caused by vasculopathy causes a switch in MR function towards a proverbial “death” receptor.

Keywords

Hypertension Mineralocorticoid receptor Microglia Neuroinflammation 

Notes

Acknowledgements

Work described in this review was supported by the Ministry of Science and Technology (PICTs 2012-0009 and 2012-0820), the National Research Council of Argentina (PIP 112 20120100016), the University of Buenos Aires (Ubacyt 20020130100418BA) and Roemmers and Williams Foundations. The MR antibody # 365-4D6 was generously provided by Dr. E. Gomez-Sanchez and Dr. C. Gomez Sanchez (Endocrine Section, G.V. (Sonny) Montgomery, VA Medical Center, Departments of Medicine, Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, USA). CORT113176 was provided by CORCEPT Therapeutics, Menlo Park, CA, USA. The technical assistance of Mrs. Analia Lima and Paulina Roig is gratefully acknowledged.

Author Contributions

MEB and LP performed the work and designed the figures; ERK reviewed the manuscript, AFN wrote the paper.

Compliance with Ethical Standards

Conflict of interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. 1.Laboratory of Neuroendocrine BiochemistryInstituto de Biologia y Medicina Experimental-CONICETBuenos AiresArgentina
  2. 2.Department of Human Biochemistry, Faculty of MedicineUniversity of Buenos AiresBuenos AiresArgentina
  3. 3.Division of Endocrinology, Department of Internal MedicineLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Laboratory of Neuroactive SteroidsCajal Institute, CSICMadridSpain

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