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 |
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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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