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

摘要: Strokes are one of the leading causes mortality and chronic morbidity in world, yet with only limited successful interventions available at present. Our previous studies revealed potential role glucocorticoid receptor (GR) pathogenesis neonatal hypoxic-ischemic encephalopathy (HIE). In present study, we investigate effect GR knockdown on acute ischemic brain injuries a model focal cerebral ischemia induced by middle artery occlusion (MCAO) adult male CD1 mice. siRNAs negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The infarction volume neurobehavioral deficits determined after RT-qPCR was employed assess inflammation-related gene expression profiles before Western Blotting used evaluate levels GR, mineralocorticoid (MR) brain-derived neurotrophic factor/tropomyosin kinase B (BDNF/TrkB) signaling. treatment decreased but not MR, protein expression, significantly enhanced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) brain. Of interest, suppressed BDNF/TrkB signaling mice brains. Importantly, siRNA pretreatment increased size exacerbated MCAO comparison group. Thus, study demonstrates important regulation inflammatory responses pathway mice, revealing new insight into therapeutic strokes.