Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.
Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models. Male rats which underwent permanent middle cerebral artery occlusion were treated with a combination of estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post-ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive neurons, levels of synapse-associated proteins and activity levels of PI3K/Akt/GSK3/β-catenin survival pathway. Also, primary cortical neurons were subjected to oxygen and glucose deprivation for 17 h and returned to a normal environment in the presence of estradiol or estradiol/progesterone. Cell viability was evaluated, and activity levels of the PI3K/Akt/GSK3/β-catenin pathway. Our results indicate that some beneficial effects of estradiol were abolished in the presence of progesterone, particularly in the cerebral cortex (core). However, the combinatorial treatment showed positive effects in the hippocampus.
Departamento de Biología (Unidad Docente Fisiología Animal), Universidad Autónoma de Madrid, C/Darwin 2, 28049, Madrid, Spain.|Centro de Biología Molecular "Severo Ochoa". CSIC-UAM, C/ Nicolas Cabrera 1, 28049, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Maria Jose
MJ
Perez-Alvarez
Centro de Biología Molecular "Severo Ochoa". CSIC-UAM, C/ Nicolas Cabrera 1, 28049, Madrid, Spain.|Centro Nacional de Biotecnología. CSIC-CNB, C/ Darwin 3, 28049, Madrid, Spain.
Laura
L
Mateos
Departamento de Biología (Unidad Docente Fisiología Animal), Universidad Autónoma de Madrid, C/Darwin 2, 28049, Madrid, Spain.
Alvaro
A
Alonso
Centro de Biología Molecular "Severo Ochoa". CSIC-UAM, C/ Nicolas Cabrera 1, 28049, Madrid, Spain. fwandosell@cbm.csic.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. fwandosell@cbm.csic.es.
Francisco
F
Wandosell
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D011374:Progesterone; D004958:Estradiol
Estradiol; Glia; Neuroprotection; OGD; Progesterone; Stroke