Research Reports - Cortisol and progesterone levels and outcomes prediction after traumatic brain injury

J Neurotrauma. 2014 Feb 6

Santarsieri M(1), Niyonkuru C, McCullough EH, Dobos JA, Dixon CE, Berga SL, Wagner AK

Abstract Despite significant advances in the management of head trauma, there
remains a lack of pharmacological treatment options for traumatic brain injury
(TBI). While progesterone clinical trials have shown promise, corticosteroid
trials have failed. The purpose of this study was to (1) characterize endogenous
cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2)
determine relationships between CSF and serum profiles, and (3) assess the
utility of these hormones as predictors of long-term outcomes. We evaluated 130
adults with severe TBI. Serum samples (n=538) and CSF samples (n=746) were
collected for 6 days post-injury, analyzed for cortisol and progesterone, and
compared with healthy controls (n=13). Hormone data were linked with clinical
data, including Glasgow Outcome Scale (GOS) scores at 6 and 12 months. Group
based trajectory (TRAJ) analysis was used to develop temporal hormone profiles
delineating distinct subpopulations. Compared with controls, CSF cortisol levels
were significantly and persistently elevated during the first week after TBI, and
high CSF cortisol levels were associated with poor outcome. As a precursor to
cortisol, progesterone mediated these effects. Serum and CSF levels for both
cortisol and progesterone were strongly correlated after TBI relative to
controls, possibly because of blood-brain barrier disruption. Also,
differentially impaired hormone transport and metabolism mechanisms after TBI,
potential de novo synthesis of steroids within the brain, and the complex
interplay of cortisol and pro-inflammatory cytokines may explain these acute
hormone profiles and, when taken together, may help shed light on why
corticosteroid trials have previously failed and why progesterone treatment after
TBI may be beneficial.

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