Epidemiology of Pediatric Traumatic Brain Injury and Hypothalamic-Pituitary Disorders in Arizona

Ortiz, J. Bryce; Sukhina, Alona S.; Balkan, Baran; Harootunian, Gevork; Adelson, P. David; Lewis, Kara Stuart; Oatman, Oliver; Subbian, Vignesh; Rowe, Rachel K.; Lifshitz, Jonathan

doi:10.3389/fneur.2019.01410

Cited by 20 publications

(21 citation statements)

References 53 publications

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“…In juvenile and aging TBI research, women and female rodents would not be actively cycling, thereby having lower circulating gonadal hormones levels, where post-menopausal women have been indicated to respond similar to males (78). However, an epidemiological study of TBI in pediatric patients indicates that endocrinopathies peak within 2 years of the initial TBI, were more prevalent in females, and were predominantly reported as precocious sexual development (79). In the geriatric population, non-survivors of TBI were more likely to be males (80).…”

Section: Sensory Hypersensitivity and Estrous Cyclicitymentioning

confidence: 99%

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission

et al. 2020

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Women approximate one-third of the annual 2.8 million people in the United States who sustain traumatic brain injury (TBI). Several clinical reports support or refute that menstrual cycle-dependent fluctuations in sex hormones are associated with severity of persisting post-TBI symptoms. Previously, we reported late-onset sensory hypersensitivity to whisker stimulation that corresponded with changes in glutamate neurotransmission at 1-month following diffuse TBI in male rats. Here, we incorporated intact age-matched naturally cycling females into the experimental design while monitoring daily estrous cycle. We hypothesized that sex would not influence late-onset sensory hypersensitivity and associated in vivo amperometric extracellular recordings of glutamate neurotransmission within the behaviorally relevant thalamocortical circuit. At 28 days following midline fluid percussion injury (FPI) or sham surgery, young adult Sprague-Dawley rats were tested for hypersensitivity to whisker stimulation using the whisker nuisance task (WNT). As predicted, both male and female rats showed significantly increased sensory hypersensitivity to whisker stimulation after FPI, with females having an overall decrease in whisker nuisance scores (sex effect), but no injury and sex interaction. In males, FPI increased potassium chloride (KCl)-evoked glutamate overflow in primary somatosensory barrel cortex (S1BF) and ventral posteromedial nucleus of the thalamus (VPM), while in females the FPI effect was discernible only within the VPM. Similar to our previous report, we found the glutamate clearance parameters were not influenced by FPI, while a sex-specific effect was evident with female rats showing a lower uptake rate constant both in S1BF and VPM and longer clearance time (in S1BF) in comparison to male rats. Fluctuations in estrous cycle were evident among brain-injured females with longer diestrus (low circulating hormone) phase of the cycle over 28 days post-TBI. Together, these findings add to growing evidence indicating both similarities and differences between sexes in a chronic response to TBI. A better understanding of the influence of gonadal hormones on behavior, Krishna et al. Sex Influences TBI-Induced Behavior and Neurotransmission neurotransmission, secondary injury and repair processes after TBI is needed both clinically and translationally, with potential impact on acute treatment, rehabilitation, and symptom management.

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Section: Sensory Hypersensitivity and Estrous Cyclicitymentioning

confidence: 99%

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission

et al. 2020

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“…Hypopituitarism is a long-term complication of TBI in pediatric patients, 72 and pituitary deficiencies have been reported following moderate-severe and mild injuries. [72][73][74] We recently demonstrated that pediatric patients with a TBI have 3.22 times the risk of a subsequent central endocrinopathy compared with the general pediatric population. 74 Aging may also represent a critical period of vulnerability, given senescence is a risk factor for the development of post-traumatic hypopituitarism.…”

Section: Discussionmentioning

confidence: 99%

“…[72][73][74] We recently demonstrated that pediatric patients with a TBI have 3.22 times the risk of a subsequent central endocrinopathy compared with the general pediatric population. 74 Aging may also represent a critical period of vulnerability, given senescence is a risk factor for the development of post-traumatic hypopituitarism. 75 Future studies should include juvenile and aged rats.…”

Section: Discussionmentioning

confidence: 99%

Mild and Moderate Traumatic Brain Injury and Repeated Stress Affect Corticosterone in the Rat

Rowe

Ortiz

Thomas

2020

Neurotrauma Reports

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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.

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“…It is not clear is whether those with acute deficiencies continue to have chronic deficiencies or whether those with chronic deficiencies develop them over time. However, pediatric TBI are 3 times more likely to have a central endocrine diagnosis compared to the uninjured population (137). Despite the necessity of proper pituitary function for normal physical and brain development, hypopituitarism continues to go unrecognized and untreated in children following TBI.…”

Section: Hormonalmentioning

confidence: 99%

Pathophysiology of Pediatric Traumatic Brain Injury

et al. 2021

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The national incidence of traumatic brain injury (TBI) exceeds that of any other disease in the pediatric population. In the United States the Centers for Disease Control and Prevention (CDC) reports 697,347 annual TBIs in children ages 0–19 that result in emergency room visits, hospitalization or deaths. There is a bimodal distribution within the pediatric TBI population, with peaks in both toddlers and adolescents. Preclinical TBI research provides evidence for age differences in acute pathophysiology that likely contribute to long-term outcome differences between age groups. This review will examine the timecourse of acute pathophysiological processes during cerebral maturation, including calcium accumulation, glucose metabolism and cerebral blood flow. Consequences of pediatric TBI are complicated by the ongoing maturational changes allowing for substantial plasticity and windows of vulnerabilities. This review will also examine the timecourse of later outcomes after mild, repeat mild and more severe TBI to establish developmental windows of susceptibility and altered maturational trajectories. Research progress for pediatric TBI is critically important to reveal age-associated mechanisms and to determine knowledge gaps for future studies.

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Epidemiology of Pediatric Traumatic Brain Injury and Hypothalamic-Pituitary Disorders in Arizona

Cited by 20 publications

References 53 publications

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission

Mild and Moderate Traumatic Brain Injury and Repeated Stress Affect Corticosterone in the Rat

Pathophysiology of Pediatric Traumatic Brain Injury

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