{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:54:56Z","timestamp":1791399296034,"version":"4.3.3"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["N642881"],"award-info":[{"award-number":["N642881"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Traumatic brain injury (TBI) causes neuroendocrine dysregulation in up to 40% of humans, which is related to impaired function of the hypothalamo-hypophyseal axis and contributes to TBI-related co-morbidities. Our objective was to investigate whether hypophyseal atrophy can be recapitulated in rat lateral fluid-percussion injury model of human TBI. High-resolution structural magnetic resonance images (MRI) were acquired from rats at 2 days and 5 months post-TBI. To measure the lobe-specific volumetric changes, manganese-enhanced MRI (MEMRI) scans were acquired from rats at 8 months post-TBI, which also underwent the pentylenetetrazol (PTZ) seizure susceptibility and Morris water-maze spatial memory tests. MRI revealed no differences in the total hypophyseal volume between TBI and controls at 2 days, 5 months or 8 months post-TBI. Surprisingly, MEMRI at 8 months post-TBI indicated a 17% reduction in neurohypophyseal volume in the TBI group as compared to controls (1.04\u2009\u00b1\u20090.05\u2009mm<jats:sup>3<\/jats:sup> vs 1.25\u2009\u00b1\u20090.05\u2009mm<jats:sup>3<\/jats:sup>, p\u2009&lt;\u20090.05). Moreover, neurohypophyseal volume inversely correlated with the number of PTZ-induced epileptiform discharges and the mean latency to platform in the Morris water-maze test. Our data demonstrate that TBI leads to neurohypophyseal lobe-specific atrophy and may serve as a prognostic biomarker for post-TBI outcome.<\/jats:p>","DOI":"10.1038\/s41598-019-48404-w","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T10:02:36Z","timestamp":1565776956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lateral fluid-percussion injury leads to pituitary atrophy in rats"],"prefix":"10.1038","volume":"9","author":[{"given":"Mehwish","family":"Anwer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"Immonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick M. E. A.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier Ekolle","family":"Ndode-Ekane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Puhakka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Gr\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asla","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"48404_CR1","unstructured":"Dewan, M. C. et al. Estimating the global incidence of traumatic brain injury. J. Neurosurg. 1\u201318 (2018)."},{"key":"48404_CR2","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/S1474-4422(08)70164-9","volume":"7","author":"AI Maas","year":"2008","unstructured":"Maas, A. I., Stocchetti, N. & Bullock, R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 7, 728\u2013741 (2008).","journal-title":"Lancet Neurol."},{"key":"48404_CR3","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1212\/WNL.59.9_suppl_5.S21","volume":"59","author":"ST Herman","year":"2002","unstructured":"Herman, S. T. Epilepsy after brain insult: targeting epileptogenesis. Neurology 59, S21\u20136 (2002).","journal-title":"Neurology"},{"key":"48404_CR4","doi-asserted-by":"crossref","unstructured":"Klein, P. et al. Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia (2017).","DOI":"10.1111\/epi.13965"},{"key":"48404_CR5","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1089\/neu.2008.0751","volume":"26","author":"BS Kasturi","year":"2009","unstructured":"Kasturi, B. S. & Stein, D. G. Traumatic Brain Injury Causes Long-Term Reduction in Serum Growth Hormone and Persistent Astrocytosis in the Cortico-Hypothalamo-Pituitary Axis of Adult Male Rats. J. Neurotrauma 26, 1315\u20131324 (2009).","journal-title":"J. Neurotrauma"},{"key":"48404_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12020-013-0049-1","volume":"45","author":"E Richmond","year":"2014","unstructured":"Richmond, E. & Rogol, A. D. Traumatic brain injury: endocrine consequences in children and adults. Endocrine 45, 3\u20138 (2014).","journal-title":"Endocrine"},{"key":"48404_CR7","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s11102-010-0235-6","volume":"15","author":"V Gasco","year":"2012","unstructured":"Gasco, V. et al. Hypopituitarism following brain injury: when does it occur and how best to test? Pituitary 15, 20\u20134 (2012).","journal-title":"Pituitary"},{"key":"48404_CR8","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3390\/jcm4051025","volume":"4","author":"F Guaraldi","year":"2015","unstructured":"Guaraldi, F., Grottoli, S., Arvat, E. & Ghigo, E. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury. J. Clin. Med. 4, 1025\u20131035 (2015).","journal-title":"J. Clin. Med."},{"key":"48404_CR9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s11102-008-0130-6","volume":"15","author":"JR Dusick","year":"2012","unstructured":"Dusick, J. R., Wang, C., Cohan, P., Swerdloff, R. & Kelly, D. F. Pathophysiology of hypopituitarism in the setting of brain injury. Pituitary 15, 2\u20139 (2012).","journal-title":"Pituitary"},{"key":"48404_CR10","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1210\/er.2014-1065","volume":"36","author":"F Tanriverdi","year":"2015","unstructured":"Tanriverdi, F. et al. Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr. Rev. 36, 305\u201342 (2015).","journal-title":"Endocr. Rev."},{"key":"48404_CR11","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.3390\/jcm4071448","volume":"4","author":"C Capatina","year":"2015","unstructured":"Capatina, C., Paluzzi, A., Mitchell, R. & Karavitaki, N. Diabetes Insipidus after Traumatic Brain Injury. J. Clin. Med. 4, 1448\u20131462 (2015).","journal-title":"J. Clin. Med."},{"key":"48404_CR12","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1089\/08977150152725669","volume":"18","author":"PL Grundy","year":"2001","unstructured":"Grundy, P. L., Harbuz, M. S., Jessop, D. S., Lightman, S. L. & Sharples, P. M. The hypothalamo-pituitary-adrenal axis response to experimental traumatic brain injury. J. Neurotrauma 18, 1373\u20131381 (2001).","journal-title":"J. Neurotrauma"},{"key":"48404_CR13","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1136\/jnnp-2016-315500","volume":"88","author":"CL Tan","year":"2017","unstructured":"Tan, C. L. et al. The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance. J Neurol Neurosurg Psychiatry 88, 971\u2013981 (2017).","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"48404_CR14","doi-asserted-by":"crossref","unstructured":"Booij, H. A., Gaykema, W. D. C., Kuijpers, K. A. J., Pouwels, M. J. M. & Den Hertog, H. M. Pituitary dysfunction and association with fatigue in stroke and other acute brain injury (2018).","DOI":"10.1530\/EC-18-0147"},{"key":"48404_CR15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.yebeh.2014.01.013","volume":"38","author":"A Pitk\u00e4nen","year":"2014","unstructured":"Pitk\u00e4nen, A. et al. Posttraumatic epilepsy - disease or comorbidity? Epilepsy Behav. 38, 19\u201324 (2014).","journal-title":"Epilepsy Behav."},{"issue":"Suppl 17","key":"48404_CR16","first-page":"41","volume":"62","author":"R Yehuda","year":"2001","unstructured":"Yehuda, R. Biology of posttraumatic stress disorder. J. Clin. Psychiatry 62(Suppl 17), 41\u20136 (2001).","journal-title":"J. Clin. Psychiatry"},{"key":"48404_CR17","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.physbeh.2016.05.015","volume":"166","author":"AC Wulsin","year":"2016","unstructured":"Wulsin, A. C., Solomon, M. B., Privitera, M. D., Danzer, S. C. & Herman, J. P. Hypothalamic-pituitary-adrenocortical axis dysfunction in epilepsy. Physiol. Behav. 166, 22\u201331 (2016).","journal-title":"Physiol. Behav."},{"key":"48404_CR18","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1089\/neu.2015.3981","volume":"33","author":"A Kleindienst","year":"2015","unstructured":"Kleindienst, A., Hannon, M. J., Buchfelder, M. & Verbalis, J. G. Hyponatremia in Neurotrauma: The Role of Vasopressin. J. Neurotrauma 33, 615\u2013624 (2015).","journal-title":"J. Neurotrauma"},{"key":"48404_CR19","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1097\/RCT.0b013e3181636ed4","volume":"32","author":"DD Makulski","year":"2008","unstructured":"Makulski, D. D., Taber, K. H. & Chiou-Tan, F. Y. Neuroimaging in posttraumatic hypopituitarism. J. Comput. Assist. Tomogr. 32, 324\u20138 (2008).","journal-title":"J. Comput. Assist. Tomogr."},{"key":"48404_CR20","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1210\/en.2018-00203","volume":"159","author":"AL Russell","year":"2018","unstructured":"Russell, A. L. et al. Differential Responses of the HPA Axis to Mild Blast Traumatic Brain Injury in Male and Female Mice. Endocrinology 159, 2363\u20132375 (2018).","journal-title":"Endocrinology"},{"key":"48404_CR21","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1089\/neu.2013.2990","volume":"30","author":"T Greco","year":"2013","unstructured":"Greco, T., Hovda, D. & Prins, M. The Effects of Repeat Traumatic Brain Injury on the Pituitary in Adolescent Rats. J. Neurotrauma 30, 1983\u20131990 (2013).","journal-title":"J. Neurotrauma"},{"key":"48404_CR22","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.neuroimage.2004.03.031","volume":"22","author":"I Aoki","year":"2004","unstructured":"Aoki, I., Wu, Y.-J. L., Silva, A. C., Lynch, R. M. & Koretsky, A. P. In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI. Neuroimage 22, 1046\u20131059 (2004).","journal-title":"Neuroimage"},{"key":"48404_CR23","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/nbm.945","volume":"17","author":"AC Silva","year":"2004","unstructured":"Silva, A. C., Lee, J. H., Aoki, I. & Koretsky, A. P. Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations. NMR Biomed. NMR Biomed 17, 532\u2013543 (2004).","journal-title":"NMR Biomed. NMR Biomed"},{"key":"48404_CR24","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/0306-4522(89)90247-9","volume":"28","author":"TK McIntosh","year":"1989","unstructured":"McIntosh, T. K. et al. Traumatic brain injury in the rat: Characterization of a lateral fluid-percussion model. Neuroscience 28, 233\u2013244 (1989).","journal-title":"Neuroscience"},{"key":"48404_CR25","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.neuroscience.2006.03.012","volume":"140","author":"I Kharatishvili","year":"2006","unstructured":"Kharatishvili, I., Nissinen, J. P., McIntosh, T. K. & Pitk\u00e4nen, A. A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats. Neuroscience 140, 685\u2013697 (2006).","journal-title":"Neuroscience"},{"key":"48404_CR26","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.expneurol.2009.01.026","volume":"217","author":"I Kharatishvili","year":"2009","unstructured":"Kharatishvili, I., Sierra, A., Immonen, R. J., Gr\u00f6hn, O. H. J. & Pitk\u00e4nen, A. Quantitative T2 mapping as a potential marker for the initial assessment of the severity of damage after traumatic brain injury in rat. Exp. Neurol. 217, 154\u2013164 (2009).","journal-title":"Exp. Neurol."},{"key":"48404_CR27","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1038\/nprot.2010.112","volume":"5","author":"SV Kabadi","year":"2010","unstructured":"Kabadi, S. V., Hilton, G. D., Stoica, B. A., Zapple, D. N. & Faden, A. I. Fluid-percussion-induced traumatic brain injury model in rats. Nature Protocols 5, 1552\u20131563 (2010).","journal-title":"Nature Protocols"},{"key":"48404_CR28","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.4103\/1673-5374.160100","volume":"10","author":"YP Lin","year":"2015","unstructured":"Lin, Y. P., Jiang, R. C. & Zhang, J. N. Stability of rat models of fluid percussion-induced traumatic brain injury: Comparison of three different impact forces. Neural Regen. Res. 10, 1088\u20131094 (2015).","journal-title":"Neural Regen. Res."},{"key":"48404_CR29","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1089\/neu.2010.1448","volume":"27","author":"NM Hayward","year":"2010","unstructured":"Hayward, N. M. et al. Association of Chronic Vascular Changes with Functional Outcome after Traumatic Brain Injury in Rats. J. Neurotrauma 27, 2203\u20132219 (2010).","journal-title":"J. Neurotrauma"},{"key":"48404_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0920-1211(03)00034-2","volume":"54","author":"H Karhunen","year":"2003","unstructured":"Karhunen, H. et al. Long-term functional consequences of transient occlusion of the middle cerebral artery in rats:: A 1-year follow-up of the development of epileptogenesis and memory impairment in relation to sensorimotor deficits. Epilepsy Res. 54, 1\u201310 (2003).","journal-title":"Epilepsy Res."},{"key":"48404_CR31","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/jcbfm.2010.67","volume":"31","author":"NM Hayward","year":"2011","unstructured":"Hayward, N. M. et al. Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats. J. Cereb. Blood Flow Metab. 31, 166\u2013177 (2011).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"48404_CR32","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/j.1439-0264.2010.00995.x","volume":"39","author":"E Theunissen","year":"2010","unstructured":"Theunissen, E. et al. Detailed Visualization of the Functional Regions of the Rat Pituitary Gland by High-Resolution T2-Weighted MRI. J. Vet. Med. Ser. C Anat. Histol. Embryol. 39, 194\u2013200 (2010).","journal-title":"J. Vet. Med. Ser. C Anat. Histol. Embryol."},{"key":"48404_CR33","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1891\/0730-0832.19.2.9","volume":"19","author":"A Dorton","year":"2000","unstructured":"Dorton, A. The Pituitary Gland: Embryology, Physiology, and Pathophysiology. Neonatal Netw. 19, 9\u201317 (2000).","journal-title":"Neonatal Netw."},{"key":"48404_CR34","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s00234-018-2072-7","volume":"60","author":"NC Adams","year":"2018","unstructured":"Adams, N. C. et al. Neuroimaging of central diabetes insipidus\u2014when, how and findings. Neuroradiology 60, 995\u20131012 (2018).","journal-title":"Neuroradiology"},{"key":"48404_CR35","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1007\/s00134-007-0902-x","volume":"34","author":"B Maiya","year":"2008","unstructured":"Maiya, B. et al. Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury. Intensive Care Med. 34, 468\u2013475 (2008).","journal-title":"Intensive Care Med."},{"key":"48404_CR36","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.mri.2014.02.006","volume":"32","author":"A Daducci","year":"2014","unstructured":"Daducci, A. et al. Manganese-enhanced magnetic resonance imaging investigation of the interferon-\u03b1 model of depression in rats. Magn. Reson. Imaging 32, 529\u2013534 (2014).","journal-title":"Magn. Reson. Imaging"},{"key":"48404_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroimage.2008.11.022","volume":"45","author":"RJ Immonen","year":"2008","unstructured":"Immonen, R. J., Kharatishvili, I., Gr\u00f6hn, H., Pitk\u00e4nen, A. & Gr\u00f6hn, O. H. J. Quantitative MRI predicts long-term structural and functional outcome after experimental traumatic brain injury. Neuroimage 45, 1\u20139 (2008).","journal-title":"Neuroimage"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48404-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48404-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48404-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T12:33:21Z","timestamp":1671280401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-48404-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["48404"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-48404-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,14]]},"assertion":[{"value":"13 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11819"}}