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Inadequate Expression and Activation of Mineralocorticoid Receptor Aggravates Spatial Memory Impairment after Traumatic Brain Injury.

Research paper by Bin B Zhang, Xueli X Zhu, Liang L Wang, Zonggang Z Hou, Shuyu S Hao, Mengshi M Yang, Fei F Gao, Baiyun B Liu

Indexed on: 19 Nov '19Published on: 18 Nov '19Published in: Neuroscience



Abstract

The administration of glucocorticoids (GCs) for the treatment of traumatic brain injury (TBI) is controversial. Both protective and deleterious effects of GCs on the brain have been reported in previous studies, while the mechanisms are unclear. Most experimental studies have reported glucocorticoid receptor (GR)-mediated deleterious effects after TBI. Sufficient mineralocorticoid receptor (MR) activation was reported to be indispensable for normal function and survival of hippocampal neurons, but changes in MR expression and activation and the roles of MRs in the survival of neurons after TBI remain unclear. We hypothesized that inadequate MR expression and activation caused by TBI aggravates posttraumatic hippocampal apoptosis but that restoration by restoring MRs promotes the survival of neurons. Using a rat controlled cortical impact model, we examined plasma corticosterone, MR expression and activation, neuronal apoptosis in the hippocampus, and spatial memory on day 3 after injury with and without fludrocortisone (1 mg/kg) treatment. Plasma corticosterone levels were significantly reduced after TBI. In addition, both MR expression and activation were inhibited. Fludrocortisone treatment significantly increased both the expression and activation of MRs, reduced the number of apoptotic neurons and cell loss in the ipsilateral hippocampus, and subsequently improved spatial memory. Its protective effects were counteracted by the MR antagonist spironolactone. The results suggest that adequate expression and activation of MRs is crucial for the survival of neurons after TBI and that fludrocortisone protects hippocampal neurons via promoting MR expression and activation. Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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