title: Profiling Neuroactive Steroid Levels After Traumatic Brain Injury in Male Mice.
abstract: The incidence of traumatic brain injuries (TBIs) in humans has rapidly increased in the last ten years. The most common causes are falls and car accidents. Approximately 80 000-90 000 persons per year will suffer some permanent disability as a result of the lesion, and one of the most common symptoms is the decline of hormone levels, also known as post-TBI hormonal deficiency syndrome. This issue has become more and more important, and many studies have focused on shedding some light on it. The hormonal decline affects not only gonadal steroid hormones but also neuroactive steroids, which play an important role in TBI recovery by neuroprotective and neurotrophic actions. The present work used an adolescent close-head murine model to analyze brain and plasma neurosteroid level changes after TBI and to establish correlations with edema and neurological impairments, 2 of the hallmarks of TBI. Our results showed changes in brain pregnenolone, testosterone, dihydrotestosterone (DHT), and 3α-diol levels whereas in plasma, the changes were present in progesterone, DHT, 3α-diol, and 3β-diol. Within them, pregnenolone, progesterone, DHT, and 3α-diol levels positively correlated with edema formation and neurological score, whereas testosterone inversely correlated with these 2 variables. These findings suggest that changes in the brain levels of some neuroactive steroids may contribute to the alterations in brain function caused by the lesion and that plasma levels of some neuroactive steroids could be good candidates of blood markers to predict TBI outcome.
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Lopez-Rodriguez
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Estefania
authors.initials: E
authors.lastname: Acaz-Fonseca
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Spezzano
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giatti
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Viveros
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Melcangi
authors.affiliation: Instituto Cajal (A.B.L.-R., E.A.-F., L.M.G.-S.), Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain; Department of Animal Physiology (Animal Physiology II) (A.B.L.-R., M.-P.V.), Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; and Department of Pharmacological and Biomolecular Sciences (P.S., S.G., D.C., R.C.M.), Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, 20133 Milano, Italy.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000150:complications; D013196:Dihydrotestosterone / Q000097:blood; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000097:blood*; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D011897:Random Allocation; D013739:Testosterone / Q000097:blood; D015431:Weight Loss
chemical_list: D018377:Neurotransmitter Agents; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D011374:Progesterone; D011284:Pregnenolone