Abstract

Neonatal hypoxic‐ischemic encephalopathy (HI) is a major cause of neurologic deficits in newborns. Since administration of progesterone (PROG) has shown neuroprotective effects in adult models of nervous system injury, we evaluated the effects of PROG in a model of neonatal HI.Seven‐days‐old rats (n=6) were subjected to a surgery for ligation of the common right carotid artery followed by exposure to an hypoxic atmosphere (8% of oxygen) for 60 min. PROG (10 mg/kg) was administered before and/or after HI. Rats were euthanized one week after HI and their brains were processed for histology or Western blot analysis. Hemispheric and hippocampal volumes were measured and apoptotic cells were counted in the CA1 and CA3 areas of the hippocampus. Proteins involved in cell death and survival (caspase‐3 and Akt) were also analyzed. This study was approved by the local Institutional Animal Care and Use Committee (UFRGS #26669; HCPA #140578).The hemispheric and hippocampal lesion caused by HI was reduced by PROG treatment. The number of apoptotic cells in CA1 and CA3 areas was also decreased by PROG administration. Expression of p‐Akt was unaffected by HI but was significantly increased in the hippocampus of PROG‐treated animals. Moreover, administration of PROG reduced hippocampal cleaved caspase‐3 expression.In summary, PROG administration reduced brain damage and neuronal apoptosis in neonatal animals submitted to HI. This neuroprotective effect is probably related to the capability of PROG in regulating caspase‐3 and Akt signaling pathways.Support or Funding InformationThis study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq‐Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES‐Brazil), Pró‐Reitoria de Pesquisa (PROPESQ/UFRGS‐Brazil), and Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA‐Brazil).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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