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Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalop...

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Autores principales: Li, Yong, Huang, Lei, Ma, Qingyi, Concepcion, Katherine R., Song, Minwoo A., Zhang, Peng, Fu, Yingjie, Xiao, Daliao, Zhang, Lubo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121696/
https://www.ncbi.nlm.nih.gov/pubmed/30126083
http://dx.doi.org/10.3390/ijms19082428
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author Li, Yong
Huang, Lei
Ma, Qingyi
Concepcion, Katherine R.
Song, Minwoo A.
Zhang, Peng
Fu, Yingjie
Xiao, Daliao
Zhang, Lubo
author_facet Li, Yong
Huang, Lei
Ma, Qingyi
Concepcion, Katherine R.
Song, Minwoo A.
Zhang, Peng
Fu, Yingjie
Xiao, Daliao
Zhang, Lubo
author_sort Li, Yong
collection PubMed
description Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes.
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spelling pubmed-61216962018-09-07 Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice Li, Yong Huang, Lei Ma, Qingyi Concepcion, Katherine R. Song, Minwoo A. Zhang, Peng Fu, Yingjie Xiao, Daliao Zhang, Lubo Int J Mol Sci Article Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes. MDPI 2018-08-17 /pmc/articles/PMC6121696/ /pubmed/30126083 http://dx.doi.org/10.3390/ijms19082428 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yong
Huang, Lei
Ma, Qingyi
Concepcion, Katherine R.
Song, Minwoo A.
Zhang, Peng
Fu, Yingjie
Xiao, Daliao
Zhang, Lubo
Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title_full Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title_fullStr Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title_full_unstemmed Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title_short Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
title_sort repression of the glucocorticoid receptor aggravates acute ischemic brain injuries in adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121696/
https://www.ncbi.nlm.nih.gov/pubmed/30126083
http://dx.doi.org/10.3390/ijms19082428
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