Temporal acute serum estradiol and tumor necrosis factor-α associations and risk of death after severe traumatic brain injury

Model System:

TBI

Reference Type:

Journal article

Accession No.:

J86112

Journal:

Journal of Neurotrauma

Year, Volume, Issue, Page(s):

2020 , 37, 20, 2198-2210

Publication Website:

Abstract:

Study tested the following hypotheses: (1) a positive feedback relationship exists between acute serum tumor necrosis factor-alpha (TNFa) and estradiol (E2), and (2) acute concentrations of E2 and TNFa are prognostic indicators of death after severe traumatic brain injury (TBI). Severe TBI activates a robust systemic response that involves inflammatory and other factors, including E2, associated with increased deaths. TNFa is a significant mediator of systemic shock, and it is an extra-gonadal transcription factor for E2 production. Serum samples were collected for the first five days after injury in 157 adults with severe TBI. The TNFa and E2 levels were averaged into two time epochs: first 72 hours (T1) and second 72 hours after injury (T2). A cross-lag panel analysis conducted between T1 and T2 TNFa and E2 levels showed significant cross-lag effects: T1 TNFa and T1 E2 were related to T2 E2 and T2 TNFa, respectively. Cox proportional hazards multivariable regression models determined that increases in T1 E2 (hazard ratio [HR] = 1.79), but not T2 E2 (HR= 0.91), were associated with increased risk of death. Increased T2 TNFa (HR = 2.47), and T1 TNFa (HR = 1.47), to a lesser degree, were associated with increased risk of death. Relationships of death with T2 TNFa and T1 E2 were mediated partially by cardiovascular, hepatic, and renal dysfunction. Findings suggest that both E2 and TNFa are systemic, reciprocally related biomarkers that may be indicative of systemic compromise and increased risk of death after severe TBI.

Author(s):