Abstract
Traumatic brain injury (TBI) survivors suffer from a range of morbidities, including post-traumatic endocrinopathies that can cause physical and mental changes in patients, greatly compromising quality of life. This study tested the hypothesis that mild and moderate diffuse TBI leads to chronic deficiencies in corticosterone (CORT) regulation following repeated exposure to restraint stress over time. Young adult male rats (n = 9–11/group) were subjected to mild or moderate TBI induced by midline fluid percussion injury (mFPI) or control sham surgery. At 6 and 24 h post-injury, both mild and moderate TBI resulted in elevated resting plasma CORT levels compared with uninjured shams. Independent of TBI severity, all rats had lower resting plasma CORT levels at 7, 14, 28, and 54 days post-injury compared with pre-surgery baseline CORT. Circulating levels of CORT were also evaluated under restraint stress and in response to dexamethasone (DEX), a synthetic glucocorticoid. Independent of TBI severity, restraint stress elevated CORT at 30, 60, and 90 min post-stressor initiation at all post-injury time-points. A blunted CORT response to restraint stress was observed with lower CORT levels after restraint at 28 and 54 days compared with 7 days post-injury (DPI), indicative of habituation to the stressor. A high dose of DEX lowered CORT levels at 90 min post-restraint stress initiation compared with low-dose DEX, independent of TBI severity. These results support TBI-induced CORT dysregulation at acute time-points, but additional studies that investigate the onset and progression of endocrinopathies, controlling for habituation to repeated restraint stress, are needed to inform the diagnosis and treatment of such morbidities in TBI survivors.
Highlights
Traumatic brain injury (TBI) is initiated by a mechanical injury followed by ensuing cellular cascades that lead to the development of acute deficits and chronic morbidities.1,2 TBI survivors suffer from a range of morbidities that include post-traumatic endocrinopathies.3 endocrinopathies were once thought to be rare, they are reported over a wide range, with 2–90% of TBI survivors reporting endocrine dysregulation.3–5 Endocrinopathies can cause impairments that can substantially compromise quality of life in TBI survivors.3,6,7 The risk factors and pathophysiology of TBI-induced endocrinopathies are not yet fully understood, which limits the development and refinement of therapeutic targets and rehabilitative strategies
Diffuse TBI resulted in elevated acute CORT levels independent of stress CORT was measured: 1) at pre-surgery baseline; 2) acutely at 6 and 24 h post-injury; and 3) chronically at 7, 14, 28, and 54 days post-injury (DPI)
There were no differences in presurgery CORT levels among groups (F[2,27] = 0.545, p = 0.586; Fig. 2A)
Summary
Traumatic brain injury (TBI) is initiated by a mechanical injury followed by ensuing cellular cascades that lead to the development of acute deficits and chronic morbidities. TBI survivors suffer from a range of morbidities that include post-traumatic endocrinopathies. endocrinopathies were once thought to be rare, they are reported over a wide range, with 2–90% of TBI survivors reporting endocrine dysregulation. Endocrinopathies can cause impairments that can substantially compromise quality of life in TBI survivors. The risk factors and pathophysiology of TBI-induced endocrinopathies are not yet fully understood, which limits the development and refinement of therapeutic targets and rehabilitative strategies. Traumatic brain injury (TBI) is initiated by a mechanical injury followed by ensuing cellular cascades that lead to the development of acute deficits and chronic morbidities.. TBI survivors suffer from a range of morbidities that include post-traumatic endocrinopathies.. Endocrinopathies were once thought to be rare, they are reported over a wide range, with 2–90% of TBI survivors reporting endocrine dysregulation.. Endocrinopathies can cause impairments that can substantially compromise quality of life in TBI survivors.. The risk factors and pathophysiology of TBI-induced endocrinopathies are not yet fully understood, which limits the development and refinement of therapeutic targets and rehabilitative strategies. Pre-clinical studies that investigate the onset and progression of these endocrinopathies may provide translational insights that inform the treatment of such morbidities in TBI survivors
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