Research Papers: Pathology:

Use of estetrol with other steroids for attenuation of neonatal hypoxic-Ischemic brain injury: to combine or not to combine?

Ekaterine Tskitishvili _, Christel Pequeux, Carine Munaut, Renaud Viellevoye, Michelle Nisolle, Agnes Noël and Jean-Michel Foidart

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Oncotarget. 2016; 7:33722-33743. https://doi.org/10.18632/oncotarget.9591

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Ekaterine Tskitishvili1, Christel Pequeux1, Carine Munaut1, Renaud Viellevoye2, Michelle Nisolle3, Agnes Noël1 and Jean-Michel Foidart1

1 Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, Liege 1, Belgium

2 Neonatal Intensive Care Unit, Department of Pediatrics, University of Liege, Liege 1, Belgium

3 Department of Obstetrics and Gynecology, University of Liege, Liege1, Belgium

Correspondence to:

Ekaterine Tskitishvili, email:

Keywords: neonatal hypoxic-ischemic encephalopathy, hippocampus, cortex, estetrol, estradiol, Pathology Section

Received: March 16, 2016 Accepted: May 17, 2016 Published: May 25, 2016


Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated.The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4.

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