title: Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.
abstract: Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.
authors.affiliation: Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, Madrid, Spain. Electronic address: lranabelen@gmail.com.
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Lopez-Rodriguez
authors.affiliation: Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Estefania
authors.initials: E
authors.lastname: Acaz-Fonseca
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giatti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.affiliation: Department of Animal Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Viveros
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Melcangi
authors.affiliation: Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D051379:Mice; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D020127:Recovery of Function
chemical_list: D018377:Neurotransmitter Agents; D003687:Dehydroepiandrosterone; D011374:Progesterone
keywords: 17β-Estradiol; Dehydroepiandrosterone; Isopregnanolone; Progesterone; Testosterone; Tetrahydroprogesterone