Repression of the Glucocorticoid Receptor Increases Hypoxic-Ischemic Brain Injury in the Male Neonatal Rat

Autor: Lubo Zhang, Johnny D. Figueroa, Richard E. Hartman, Katherine R. Knox-Concepcion, Yong Li
Rok vydání: 2019
Předmět:
Male
neuroinflammation
Rats
Sprague-Dawley
lcsh:Chemistry
Glucocorticoid receptor
glucocorticoid receptor
Gait
lcsh:QH301-705.5
Spectroscopy
General Medicine
encephalopathy
Computer Science Applications
Hypoxia-Ischemia
Brain
Female
RNA Interference
neuroprotection
medicine.symptom
Glucocorticoid
medicine.drug
medicine.medical_specialty
hypoxic-ischemic
brain
Encephalopathy
Inflammation
Neuroprotection
Article
Catalysis
Proinflammatory cytokine
neonatal
Inorganic Chemistry
Receptors
Glucocorticoid
Sex Factors
Internal medicine
Reflex
medicine
Animals
Physical and Theoretical Chemistry
Rice–Vannucci
Molecular Biology
Neuroinflammation
Asphyxia
business.industry
Organic Chemistry
medicine.disease
Rats
functional outcomes
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
glucocorticoid
business
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 14, p 3493 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 14
ISSN: 1422-0067
Popis: Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia is the most common cause of neonatal brain damage and results in significant neurological sequelae, including cerebral palsy. The current therapeutic interventions are extremely limited in improving neonatal outcomes. The present study tests the hypothesis that the suppression of endogenous glucocorticoid receptors (GRs) in the brain increases hypoxic-ischemic (HI) induced neonatal brain injury and worsens neurobehavioral outcomes through the promotion of increased inflammation. A mild HI treatment of P9 rat pups with ligation of the right common carotid artery followed by the treatment of 8% O2 for 60 min produced more significant brain injury with larger infarct size in female than male pups. Intracerebroventricular injection of GR siRNAs significantly reduced GR protein and mRNA abundance in the neonatal brain. Knockdown of endogenous brain GRs significantly increased brain infarct size after HI injury in male, but not female, rat pups. Moreover, GR repression resulted in a significant increase in inflammatory cytokines TNF-&alpha
and IL-10 at 6 h after HI injury in male pups. Male pups treated with GR siRNAs showed a significantly worsened reflex response and exhibited significant gait disturbances. The present study demonstrates that endogenous brain GRs play an important role in protecting the neonatal brain from HI induced injury in male pups, and suggests a potential role of glucocorticoids in sex differential treatment of HIE in the neonate.
Databáze: OpenAIRE
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