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Steroid Profiling in Brain and Plasma of Male and Pseudopregnant Female Rats after Traumatic Brain Injury: Analysis by Gas Chromatography/Mass Spectrometry

Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 788 (D.M., A.P., P.L., B.E., A.C., M.S., R.G.), Steroids, Neuroprotection, and Neuroregeneration, and University Paris 11, 94276 Kremlin-Bicêtre, France; and Brain Research Laboratory (D.G.S.), Department of Emergency Medicine, Emory University, Atlanta, Georgia 30322

Address all correspondence and requests for reprints to: Dr. R. Guennoun, Institut National de la Santé et de la Recherche Médicale UMR788, 80 Rue du Général Leclerc, 94276 Bicêtre, France. E-mail: guennoun{at}kb.inserm.fr.

Steroids in brain arise from the peripheral endocrine glands and local synthesis. In traumatic brain injury (TBI), the endogenous circulating hormones at the time of injury are important for neuroprotection. In particular, pseudopregnant females recover better than males from TBI. We investigated the effect of pseudopregnancy and TBI on steroid levels in plasma and in three brain regions (within, adjacent, and distal to the lesion site), 6 and 24 h after prefrontal cortex injury. The following steroids were analyzed by gas chromatography/mass spectrometry: pregnenolone, progesterone, 5-dihydroprogesterone, 3,5-tetrahydroprogesterone, 3ß,5-tetrahydroprogesterone, dehydroepiandrosterone, ⁴-androstenedione, testosterone, 5-dihydrotestosterone, 3,5-tetrahydrotestosterone, 3ß,5-tetrahydrotestosterone, and 17ß-estradiol. Corticosterone was assayed in plasma to account for stress in the rats. We found different steroid profiles in brain and plasma of male and pseudopregnant female rats and specific profile changes after TBI. In sham-operated pseudopregnant females, much higher levels of progesterone, 5-dihydroprogesterone, 3,5-tetrahydroprogesterone, and 3ß,5-tetrahydroprogesterone were measured in both brain and plasma, compared with sham-operated males. Plasma levels of corticosterone were high in all groups, indicating that the surgeries induced acute stress. Six hours after TBI, the levels of pregnenolone, progesterone, and 5-dihydroprogesterone increased, and those of testosterone decreased in male brain, whereas levels of 5-dihydroprogesterone and 3ß,5-tetrahydroprogesterone increased in brain of pseudopregnant female rats. Plasma levels of 5-dihydroprogesterone did not change after TBI, suggesting a local activation of the 5-reduction pathway of progesterone in both male and pseudopregnant female brain. The significant increase in neurosteroid levels in the male brain after TBI is consistent with their role in neuroprotection. In pseudopregnant females, high levels of circulating progestagens may provide protection against TBI.