Kim, HarrisonYu, TaoVan Groen, Groen ThomasChaudry, Irshad H.Hubbard, William J.2022-10-192022-10-192016-07-29Kim, H. vd. (2017). ''Treatment of traumatic brain injury with 17 alpha-ethinylestradiol-3-sulfate in a rat model''. Journal of Neurosurgery, 127(1), 23-31.0022-3085https://doi.org/10.3171/2016.7.JNS161263https://thejns.org/view/journals/j-neurosurg/127/1/article-p23.xml1933-0693http://hdl.handle.net/11452/29152OBJECTIVE 17 alpha-ethynylestradiol-3-sulfate (EE-3-SO4) is a highly water-soluble synthetic estrogen that has an extended half-life (10 hours) over that of naturally occurring estrogen (similar to 10 minutes). In this study, EE-3-SO4 was evaluated in a lateral fluid percussion induced traumatic brain injury (TBI) model in rats. METHODS A total of 9 groups of Sprague-Dawley rats underwent craniectomy. Twenty-four hours later, lateral fluid percussion was applied to 6 groups of animals to induce TBI; the remaining 3 groups served as sham control groups. EE-3-SO4 (1 mg/kg body weight in 0.4 ml/kg body weight) or saline (vehicle control) was injected intravenously 1 hour after TBI; saline was injected in all sham animals. One day after EE-3-SO4/saline injection, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and partial brain oxygen pressure (PbtO(2)) were measured in Groups 1-3 (2 TBI groups and 1 sham group), and brain edema, diffusion axonal injury, and cerebral glycolysis were assessed in Groups 4-6 using MRI T2 mapping, diffusion tensor imaging (DTI), and FDG-PET imaging, respectively. Four days after dosing, the open-field anxiety of animals was assessed in Groups 7-9 by measuring the duration that each animal spent in the center area of an open chamber during 4 minutes of monitoring. RESULTS EE-3-SO4 significantly lowered ICP while raising CPP and PbtO(2), compared with vehicle treatment in TBI-induced animals (p < 0.05). The mean size of cerebral edema of TBI animals treated with EE-3-SO4 was 25 3 mm(3) (mean SE), which was significantly smaller than that of vehicle-treated animals (67 +/- 6 mm(3), p < 0.001). Also, EE-3-SO4 treatment significantly increased the fractional anisotropy of the white matter in the ipsilateral side (p = 0.003) and cerebral glycolysis (p = 0.014). The mean duration that EE-3-SO4 treated animals spent in the center area was 12 +/- 2 seconds, which was significantly longer than that of vehicle-treated animals (4 1 seconds; p = 0.008) but not different from that of sham animals (11 +/- 3 seconds; p > 0.05). CONCLUSIONS These data support the clinical use of EE-3-SO4 for early TBI treatment.eninfo:eu-repo/semantics/openAccessNeurosciences & neurologySurgeryBehavioral testDiffusion tensor imagingIntracranial pressurePositron emission tomographyT2 mappingTBITraumatic brain injuryOrgans therapeutic approachDiffuse axonal injuryEthinyl estradiolOral-contraceptivesMu-gEstrogenPharmacokineticsParametersNeuroprotectionHippocampusAnimalsBrain injuries, traumaticDisease models, animalEthinyl estradiolExploratory behaviorMaleRatsRats sprague dawleyArticle0004040875000042-s2.0-850217657002331127127662529Clinical neurologySurgeryPyometra; Dog; Deslorelin17alpha ethinylestradiol 3 sulfateEstradiol derivativeFluorodeoxyglucoseUnclassified drugEthinyl estradiol-17-sulfateEthinylestradiolAnimal experimentAnimal modelArticleAxonal injuryBrain edemaBrain perfusionBrain regionCerebral glycolysisControlled studyDiffusion axonal injuryDiffusion tensor imagingFractional anisotropyGlycolysisIntracranial pressureMaleNonhumanOxygen tensionPartial brain oxygen pressurePerfusion pressurePositron emission tomographyPriority journalRatTraumatic brain injuryAnalogs and derivativesAnimalDisease modelDrug effectExploratory behaviorSprague Dawley ratTraumatic brain injury