title: Estetrol attenuates neonatal hypoxic-ischemic brain injury.
abstract: Estetrol (E4) is a recently described natural estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. It has important antioxidative activity. The aim of the present study was to define the importance of E4 in the attenuation of neonatal hypoxic-ischemic encephalopathy. Antioxidative effect of 650μM, 3.25mM and 6.5mM E4 on primary hippocampal cell cultures was studied before/after H202-induced oxidative stress. To examine oxidative stress and cell viability, lactate dehydrogenase activity and cell proliferation colorimetric assays were performed. To study the neuroprotective and therapeutic effects of E4 in vivo neonatal hypoxic-ischemic encephalopathy model of 7-day-old newborn rat pups was used. The neuroprotective and therapeutic effects of estetrol before/after hypoxic-ischemic insult was studied in 1mg/kg/day, 5mg/kg/day, 10mg/kg/day, 50mg/kg/day E4 pretreated/treated groups and compared with the sham and the vehicle treated groups. The body temperature of the rat pups was examined along with their body and brain weights. Brains were studied at the level of the hippocampus and cortex. Intact cell counting and expressions of microtubule-associated protein-2, doublecortin and vascular-endothelial growth factor were evaluated by histo- and immunohistochemistry. ELISAs were performed on blood samples to detect concentrations of S100B and glial fibrillary acidic protein as brain damage markers. This work reveals for the first time that E4 significantly decreases LDH activity and enhances cell proliferation in primary hippocampal neuronal cell cultures in vitro, and decreases the early gray matter loss and promotes neuro- and angiogenesis in vivo.
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: ekaterinet@hotmail.com.
authors: Ekaterine
authors: E
authors: Tskitishvili
authors: Department of Obstetrics and Gynecology, University of Liege, CHR de la CITADELLE, Boulevard du 12ème de Ligne, 4000 Liege 1, Belgium. Electronic address: michelle.nisolle@chrcitadelle.be.
authors: Michelle
authors: M
authors: Nisolle
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: c.munaut@ulg.ac.be.
authors: Carine
authors: C
authors: Munaut
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: c.pequeux@ulg.ac.be.
authors: Christel
authors: C
authors: Pequeux
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: celine.gerard@ulg.ac.be.
authors: Celine
authors: C
authors: Gerard
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: agnes.noel@ulg.ac.be.
authors: Agnes
authors: A
authors: Noel
authors: Laboratory of Development Biology and Tumor, GIGA-Cancer, Department of Obstetrics and Gynecology/Department of Clinical Sciences, University of Liege, CHU, B-23, Avenue de l'Hôpital 3, 4000 Liege 1, Belgium. Electronic address: jmfoidart@ulg.ac.be.
authors: Jean-Michel
authors: JM
authors: Foidart
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D004953:Estetrol / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D016877:Oxidants; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D004953:Estetrol
keywords: Cortex; GFAP; Hippocampus; S100B; VEGF