Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783352528803463168 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6121696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liyong repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT huanglei repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT maqingyi repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT concepcionkatheriner repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT songminwooa repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT zhangpeng repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT fuyingjie repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT xiaodaliao repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice AT zhanglubo repressionoftheglucocorticoidreceptoraggravatesacuteischemicbraininjuriesinadultmice |