title: Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.
abstract: Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.
authors.affiliation: INSERM Unité 661 (G.O., T.E.Y., N.Co., N.R., A.G., M.S., N.Ch., E.G., P.M., P.-F.M.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 5203 (G.O., T.E.Y., N.R., N.Co., A.G., M.S., N.Ch., E.G., P.M., P.-F.M.), Institut de Génomique Fonctionelle, 34094 Montpellier, France; Université Montpellier 1, 2 (G.O., T.E.Y., N.R., N.Co., A.G., M.S., N.Ch., E.G., P.M., P.-F.M.), 34967 Montpellier, France; Division of Molecular Neuroendocrinology (D.C., I.C.A.F.R.), Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom; Royal College of Surgeons in Ireland (G.O., T.E.Y., M.S., N.P.), Dublin 2, Ireland; INSERM Unité 837 (F.L., C.V., B.D., V.P.), Department of Development and Plasticity of the Postnatal Brain, Jean-Pierre Aubert Research Center, 59045 Lille, France; and University of Lille 2 (F.L., C.V., B.D., V.P.), 59000 Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Osterstock
authors.forename: Taoufik
authors.initials: T
authors.lastname: El Yandouzi
authors.forename: Nicola
authors.initials: N
authors.lastname: Romanò
authors.forename: Danielle
authors.initials: D
authors.lastname: Carmignac
authors.forename: Fanny
authors.initials: F
authors.lastname: Langlet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Coutry
authors.forename: Anne
authors.initials: A
authors.lastname: Guillou
authors.forename: Marie
authors.initials: M
authors.lastname: Schaeffer
authors.forename: Norbert
authors.initials: N
authors.lastname: Chauvet
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vanacker
authors.forename: Evelyne
authors.initials: E
authors.lastname: Galibert
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dehouck
authors.forename: Iain C A F
authors.initials: IC
authors.lastname: Robinson
authors.forename: Vincent
authors.initials: V
authors.lastname: Prévot
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Méry
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007018:Hypopituitarism / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008473:Median Eminence / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010539:Permeability; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020542:Third Ventricle / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D013007:Growth Hormone-Releasing Hormone