Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: A case series analysis

Ranganathan, Prerna; Kumar, Raj G.; Davis, Kendra; McCullough, Emily H.; Berga, Sarah L.; Wagner, Amy K.

doi:10.3109/02699052.2016.1144081

Cited by 36 publications

(23 citation statements)

References 50 publications

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“…Age can affect many different biomarkers, including stress hormones (Wagner et al, 2011a; Santarsieri et al, 2014; Ranganathan et al, 2016), sex hormones (Ranganathan et al, 2016), inflammation (Kumar et al, 2016), and BDNF (Failla et al, 2015). Experimental models show decreased BDNF mRNA, BDNF protein, and TrkB.FL mRNA in many different brain regions with older age (Romanczyk et al, 2002; Webster et al, 2006; Erickson et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

Munoz

Kumar

et al. 2017

Front. Mol. Neurosci.

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Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0–6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in “younger patients” (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

Munoz

Kumar

et al. 2017

Front. Mol. Neurosci.

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“…Inhibition of the LH surge has also been documented in mice following psychosocial stress [ 29 ]. Severe illness and traumatic brain injury in post-menopausal women have been associated with a reduction of LH and FSH levels [ 30 , 31 ]. These data further support the inhibitory effects of stress on reproductive function.…”

Section: The Impacts Of Stress Throughout the Hpg Axismentioning

confidence: 99%

Stress and the HPA Axis: Balancing Homeostasis and Fertility

Joseph

Whirledge

2017

IJMS

180

110

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An organism’s reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic–pituitary–adrenal (HPA) axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development.

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“…The beneficial and detrimental effects of cortisol elevations provide a robust exemplar of the existence of regulatory cross-talk within the humoral triad, is a significant mediator of dysfunction in both neuroinflammation (Santarsieri et al, 2015) and BDNF expression (Munoz et al, 2017). Also, in pre-menopausal women, chronically elevated cortisol may contribute to amenorrhea and menstrual cycle dysfunction (Ranganathan et al, 2016), and acute increases in cortisol are associated with long-term cognitive impairments .…”

Section: Hormonesmentioning

confidence: 99%

TBI Rehabilomics Research: Conceptualizing a humoral triad for designing effective rehabilitation interventions

Wagner

Kumar

2019

Neuropharmacology

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Most areas of medicine use biomarkers in some capacity to aid in understanding how personal biology informs clinical care. This article draws upon the Rehabilomics research model as a translational framework for programs of precision rehabilitation and intervention research focused on linking personal biology to treatment response using biopsychosocial constructs that broadly represent function and that can be applied to many clinical populations with disability. The summary applies the Rehabilomics research framework to the population with traumatic brain injury (TBI) and emphasizes a broad vision for biomarker inclusion, beyond typical brain-derived biomarkers, to capture and/or reflect important neurological and non-neurological pathology associated with TBI as a chronic condition. Humoral signaling molecules are explored as important signaling and regulatory drivers of these chronic conditions and their impact on function. Importantly, secondary injury cascades involved in the humoral triad are influenced by the systemic response to TBI and the development of non-neurological organ dysfunction (NNOD). Biomarkers have been successfully leveraged in other medical fields to inform pre-randomization patient selection for clinical trials, however, this practice largely has not been utilized in TBI research. As such, the applicability of the Rehabilomics research model to contemporary clinical trials and comparative effectiveness research designs for neurological and rehabilitation populations is emphasized. Potential points of intervention to modify inflammation, hormonal, or neurotrophic support through rehabilitation interventions are discussed.

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Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: A case series analysis

Cited by 36 publications

References 50 publications

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

Stress and the HPA Axis: Balancing Homeostasis and Fertility

TBI Rehabilomics Research: Conceptualizing a humoral triad for designing effective rehabilitation interventions

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