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Published in: Pituitary 3/2019

01-06-2019 | Central Nervous System Trauma

Traumatic brain injury and resultant pituitary dysfunction: insights from experimental animal models

Authors: Annelies Vennekens, Hugo Vankelecom

Published in: Pituitary | Issue 3/2019

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Abstract

Purpose

Traumatic brain injury (TBI) is a major worldwide cause of disability, often burdening young people with serious lifelong health problems. A frequent clinical complication is post-traumatic hypopituitarism (PTHP) manifesting in several hypothalamus-pituitary axes. The head trauma-induced mechanisms underlying PTHP remain largely unknown. Several hypotheses have been proposed including direct damage to the pituitary gland and hypothalamus, vascular events and autoimmunity. This review aims to provide a summary of the currently limited number of studies exploring hypothalamus-pituitary dysfunction in experimental animal TBI models.

Results

Although the impact of different forms of TBI on a number of hypothalamus-pituitary axes has been investigated, consequences for pituitary tissue and function have only scarcely been described. Moreover, mechanisms underlying the endocrine dysfunctions remain under explored.

Conclusions

Studies on TBI-induced pituitary dysfunction are still scarce. More research is needed to acquire mechanistic insights into the pathophysiology of PTHP which may eventually open up the horizon toward better treatments, including pituitary-regenerative approaches.
Literature
1.
go back to reference Faul M, Xu L, Wald MM, Coronado VG (2010) Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. https://www.cdc.gov/TraumaticBrainInjury. Accessed 7 Dec 2018 Faul M, Xu L, Wald MM, Coronado VG (2010) Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. https://​www.​cdc.​gov/​TraumaticBrainIn​jury. Accessed 7 Dec 2018
2.
go back to reference Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 1:1–18 Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 1:1–18
3.
go back to reference Pervez M, Kitagawa RS, Chang TR (2018) Definition of traumatic brain injury, neurosurgery, trauma orthopedics, neuroimaging, psychology, and psychiatry in mild traumatic brain injury. Neuroimaging Clin N Am 28:1–13CrossRefPubMed Pervez M, Kitagawa RS, Chang TR (2018) Definition of traumatic brain injury, neurosurgery, trauma orthopedics, neuroimaging, psychology, and psychiatry in mild traumatic brain injury. Neuroimaging Clin N Am 28:1–13CrossRefPubMed
4.
go back to reference Cyran E (1918) Hypophysenschädigung durch Schädelbasisfraktur. Dtsch Med Wochenschr 44:1261 Cyran E (1918) Hypophysenschädigung durch Schädelbasisfraktur. Dtsch Med Wochenschr 44:1261
5.
go back to reference Tanriverdi F, Schneider HJ, Aimaretti G, Masel BE, Casanueva FF, Kelestimur F (2015) Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr Rev 36:305–342CrossRefPubMed Tanriverdi F, Schneider HJ, Aimaretti G, Masel BE, Casanueva FF, Kelestimur F (2015) Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr Rev 36:305–342CrossRefPubMed
6.
go back to reference Benvenga S, Campenní A, Ruggeri RM, Trimarchi F (2000) Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85:1353–1361CrossRefPubMed Benvenga S, Campenní A, Ruggeri RM, Trimarchi F (2000) Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85:1353–1361CrossRefPubMed
7.
go back to reference Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ (2001) Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86:2752–2756PubMed Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ (2001) Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86:2752–2756PubMed
8.
go back to reference Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A (2007) Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 298:1429–1438CrossRefPubMed Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A (2007) Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 298:1429–1438CrossRefPubMed
9.
go back to reference Tan CL, Alavi SA, Baldeweg SE, Belli A, Carson A, Feeney C, Goldstone AP, Greenwood R, Menon DK, Simpson HL, Toogood AA, Gurnell M, Hutchinson PJ (2017) The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance. J Neurol Neurosurg Psychiatry 88:971–981CrossRefPubMedPubMedCentral Tan CL, Alavi SA, Baldeweg SE, Belli A, Carson A, Feeney C, Goldstone AP, Greenwood R, Menon DK, Simpson HL, Toogood AA, Gurnell M, Hutchinson PJ (2017) The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance. J Neurol Neurosurg Psychiatry 88:971–981CrossRefPubMedPubMedCentral
10.
go back to reference Kokshoorn NE, Wassenaar MJ, Biermasz NR, Roelfsema F, Smit JW, Romijn JA, Pereira AM (2010) Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values. Eur J Endocrinol 162:11–18CrossRefPubMed Kokshoorn NE, Wassenaar MJ, Biermasz NR, Roelfsema F, Smit JW, Romijn JA, Pereira AM (2010) Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values. Eur J Endocrinol 162:11–18CrossRefPubMed
11.
12.
go back to reference Fu Q, Gremeaux L, Luque RM, Liekens D, Chen J, Buch T, Waisman A, Kineman R, Vankelecom H (2012) The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration. Endocrinology 153:3224–3235CrossRefPubMed Fu Q, Gremeaux L, Luque RM, Liekens D, Chen J, Buch T, Waisman A, Kineman R, Vankelecom H (2012) The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration. Endocrinology 153:3224–3235CrossRefPubMed
13.
go back to reference Fu Q, Vankelecom H (2012) Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation. Stem Cells Dev 21:3245–3257CrossRefPubMed Fu Q, Vankelecom H (2012) Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation. Stem Cells Dev 21:3245–3257CrossRefPubMed
14.
go back to reference Willems C, Fu Q, Roose H, Mertens F, Cox B, Chen J, Vankelecom H (2016) Regeneration in the pituitary after cell-ablation injury: time-related aspects and molecular analysis. Endocrinology 157:705–721CrossRefPubMed Willems C, Fu Q, Roose H, Mertens F, Cox B, Chen J, Vankelecom H (2016) Regeneration in the pituitary after cell-ablation injury: time-related aspects and molecular analysis. Endocrinology 157:705–721CrossRefPubMed
15.
go back to reference Briones TL (2015) Animal models of traumatic brain injury: Is there an optimal model that parallels human brain injury? In: Conley YP (ed) Annual review of nursing research, vol 33. Springer, New York, pp 31–73 Briones TL (2015) Animal models of traumatic brain injury: Is there an optimal model that parallels human brain injury? In: Conley YP (ed) Annual review of nursing research, vol 33. Springer, New York, pp 31–73
16.
go back to reference Lifshitz J (2008) Fluid percussion injury model. In: Chen J, Xu ZC, Xu X-M, Zhang JH (eds) Animal models of acute neurological injuries. Humana Press, New York, pp 369–384 Lifshitz J (2008) Fluid percussion injury model. In: Chen J, Xu ZC, Xu X-M, Zhang JH (eds) Animal models of acute neurological injuries. Humana Press, New York, pp 369–384
17.
go back to reference Roe SY, McGowan EM, Rothwell NJ (1998) Evidence for the involvement of corticotrophin-releasing hormone in the pathogenesis of traumatic brain injury. Eur J Neurosci 10:553–559CrossRefPubMed Roe SY, McGowan EM, Rothwell NJ (1998) Evidence for the involvement of corticotrophin-releasing hormone in the pathogenesis of traumatic brain injury. Eur J Neurosci 10:553–559CrossRefPubMed
18.
go back to reference Grundy PL, Harbuz MS, Jessop DS, Lightman SL, Sharples PM (2001) The hypothalamo-pituitary-adrenal axis response to experimental traumatic brain injury. J Neurotrauma 18:1373–1381CrossRefPubMed Grundy PL, Harbuz MS, Jessop DS, Lightman SL, Sharples PM (2001) The hypothalamo-pituitary-adrenal axis response to experimental traumatic brain injury. J Neurotrauma 18:1373–1381CrossRefPubMed
20.
go back to reference Bouzarth WF, Shenkin HA, Feldman W (1968) Adrenocortical response to craniocerebral trauma. Surg Gynecol Obstet 126:995–1001PubMed Bouzarth WF, Shenkin HA, Feldman W (1968) Adrenocortical response to craniocerebral trauma. Surg Gynecol Obstet 126:995–1001PubMed
21.
go back to reference Griesbach GS, Hovda DA, Tio DL, Taylor AN (2011) Heightening of the stress response during the first weeks after a mild traumatic brain injury. Neuroscience 178:147–158CrossRefPubMedPubMedCentral Griesbach GS, Hovda DA, Tio DL, Taylor AN (2011) Heightening of the stress response during the first weeks after a mild traumatic brain injury. Neuroscience 178:147–158CrossRefPubMedPubMedCentral
22.
go back to reference Bornstein SR, Engeland WC, Ehrhart-Bornstein M, Herman JP (2008) Dissociation of ACTH and glucocorticoids. Trends Endocrinol Metab 19:175–180CrossRefPubMed Bornstein SR, Engeland WC, Ehrhart-Bornstein M, Herman JP (2008) Dissociation of ACTH and glucocorticoids. Trends Endocrinol Metab 19:175–180CrossRefPubMed
23.
go back to reference Rowe RK, Rumney BM, May HG, Permana P, Adelson PD, Harman SM, Lifshitz J, Thomas TC (2016) Diffuse traumatic brain injury affects chronic corticosterone function in the rat. Endocr Connect 5:152–166CrossRefPubMedPubMedCentral Rowe RK, Rumney BM, May HG, Permana P, Adelson PD, Harman SM, Lifshitz J, Thomas TC (2016) Diffuse traumatic brain injury affects chronic corticosterone function in the rat. Endocr Connect 5:152–166CrossRefPubMedPubMedCentral
25.
go back to reference Kopczak A, Kilimann I, Von Rosen F, Krewer C, Schneider HJ, Stalla GK, Schneider M (2014) Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage. J Neurotrauma 31:99–107CrossRefPubMed Kopczak A, Kilimann I, Von Rosen F, Krewer C, Schneider HJ, Stalla GK, Schneider M (2014) Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage. J Neurotrauma 31:99–107CrossRefPubMed
26.
go back to reference Taylor AN, Rahman SU, Sanders NC, Tio DL, Prolo P, Sutton RL (2008) Injury severity differentially affects short- and long-term neuroendocrine outcomes of traumatic brain injury. J Neurotrauma 25:311–323CrossRefPubMed Taylor AN, Rahman SU, Sanders NC, Tio DL, Prolo P, Sutton RL (2008) Injury severity differentially affects short- and long-term neuroendocrine outcomes of traumatic brain injury. J Neurotrauma 25:311–323CrossRefPubMed
27.
go back to reference Taylor AN, Rahman SU, Tio DL, Sanders MJ, Bando JK, Truong AH, Prolo P (2006) Lasting neuroendocrine-immune effects of traumatic brain injury in rats. J Neurotrauma 23:1802–1813CrossRefPubMed Taylor AN, Rahman SU, Tio DL, Sanders MJ, Bando JK, Truong AH, Prolo P (2006) Lasting neuroendocrine-immune effects of traumatic brain injury in rats. J Neurotrauma 23:1802–1813CrossRefPubMed
28.
go back to reference Osterstock G, El Yandouzi T, Romanò N, Carmignac D, Langlet F, Country N, Guillou A, Schaeffer M, Chauvet N, Vanacker C, Galibert E, Dehouck B, Robinson IC, Prévot V, Mollard P, Plesnila N, Méry PF (2014) Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice. Endocrinology 155:1887–1898CrossRefPubMed Osterstock G, El Yandouzi T, Romanò N, Carmignac D, Langlet F, Country N, Guillou A, Schaeffer M, Chauvet N, Vanacker C, Galibert E, Dehouck B, Robinson IC, Prévot V, Mollard P, Plesnila N, Méry PF (2014) Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice. Endocrinology 155:1887–1898CrossRefPubMed
29.
go back to reference Kasturi BS, Stein DG (2009) 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 26:1315–1324CrossRefPubMedPubMedCentral Kasturi BS, Stein DG (2009) 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 26:1315–1324CrossRefPubMedPubMedCentral
30.
go back to reference Kelly DF, McArthur DL, Levin H, Swimmer S, Dusick JR, Cohan P, Wang C, Swerdloff R (2006) Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma 23:928–942CrossRefPubMed Kelly DF, McArthur DL, Levin H, Swimmer S, Dusick JR, Cohan P, Wang C, Swerdloff R (2006) Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma 23:928–942CrossRefPubMed
31.
go back to reference Lavrnja I, Trifunovic S, Ajdzanovic V, Pekovic S, Bjelobaba I, Stojiljkovic M, Milosevic V (2014) Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study. Physiol Behav 125:30–37CrossRefPubMed Lavrnja I, Trifunovic S, Ajdzanovic V, Pekovic S, Bjelobaba I, Stojiljkovic M, Milosevic V (2014) Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study. Physiol Behav 125:30–37CrossRefPubMed
32.
go back to reference Lavrnja I, Ajdzanovic V, Trifunovic S, Savic D, Milosevic V, Stojiljkovic M, Pekovic S (2014) Cortical ablation induces time-dependent changes in rat pituitary somatotrophs and upregulates growth hormone receptor expression in the injured cortex. J Neurosci Res 92:1338–1349CrossRefPubMed Lavrnja I, Ajdzanovic V, Trifunovic S, Savic D, Milosevic V, Stojiljkovic M, Pekovic S (2014) Cortical ablation induces time-dependent changes in rat pituitary somatotrophs and upregulates growth hormone receptor expression in the injured cortex. J Neurosci Res 92:1338–1349CrossRefPubMed
34.
go back to reference Shohami E, Bass R, Trembovler V, Weidenfeld J (1995) The effect of the adrenocortical axis upon recovery from closed head injury. J Neurotrauma 12:1069–1077CrossRefPubMed Shohami E, Bass R, Trembovler V, Weidenfeld J (1995) The effect of the adrenocortical axis upon recovery from closed head injury. J Neurotrauma 12:1069–1077CrossRefPubMed
35.
go back to reference McDaniel WF (1993) The influences of fragments and analogs of ACTH/MSH upon recovery from nervous system injury. Behav Brain Res 56:11–22CrossRefPubMed McDaniel WF (1993) The influences of fragments and analogs of ACTH/MSH upon recovery from nervous system injury. Behav Brain Res 56:11–22CrossRefPubMed
36.
37.
go back to reference Ives JC, Alderman M, Stred SE (2007) Hypopituitarism after multiple concussions: a retrospective case study in an adolescent male. J Athl Train 42:431–439PubMedPubMedCentral Ives JC, Alderman M, Stred SE (2007) Hypopituitarism after multiple concussions: a retrospective case study in an adolescent male. J Athl Train 42:431–439PubMedPubMedCentral
38.
go back to reference Greco T, Hovda DA, Prins ML (2015) Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats. Dev Neurobiol 75:193–202CrossRefPubMed Greco T, Hovda DA, Prins ML (2015) Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats. Dev Neurobiol 75:193–202CrossRefPubMed
39.
go back to reference Tan H, Yang W, Wu C, Liu B, Lu H, Wang H, Yan H (2017) Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI. Sci Rep 7:3805CrossRefPubMedPubMedCentral Tan H, Yang W, Wu C, Liu B, Lu H, Wang H, Yan H (2017) Assessment of the role of intracranial hypertension and stress on hippocampal cell apoptosis and hypothalamic-pituitary dysfunction after TBI. Sci Rep 7:3805CrossRefPubMedPubMedCentral
40.
go back to reference Russell AL, Richardson MR, Bauman BM, Hernandez IM, Saperstein S, Handa RJ, Wu TJ (2018) Differential responses of the HPA axis to mild blast traumatic brain injury in male and female mice. Endocrinology 2363:2375 Russell AL, Richardson MR, Bauman BM, Hernandez IM, Saperstein S, Handa RJ, Wu TJ (2018) Differential responses of the HPA axis to mild blast traumatic brain injury in male and female mice. Endocrinology 2363:2375
Metadata
Title
Traumatic brain injury and resultant pituitary dysfunction: insights from experimental animal models
Authors
Annelies Vennekens
Hugo Vankelecom
Publication date
01-06-2019
Publisher
Springer US
Published in
Pituitary / Issue 3/2019
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-019-00961-z

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