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Progesterone in the clinical treatment of acute traumatic brain injury

, PhD & , MD FACEP
Pages 847-857 | Published online: 20 May 2010

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Ali Nouri, Farzaneh Hashemzadeh, Amin Soltani, Elham Saghaei & Hossein Amini-Khoei. (2020) Progesterone exerts antidepressant-like effect in a mouse model of maternal separation stress through mitigation of neuroinflammatory response and oxidative stress. Pharmaceutical Biology 58:1, pages 64-71.
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Rebecca Shisler Marshall & Bijoyaa Mohapatra. (2017) Integrative intervention: a new perspective and brief review in aphasia. Disability and Rehabilitation 39:19, pages 1999-2009.
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Irene Paterniti, Marika Cordaro, Michele Navarra, Emanuela Esposito & Salvatore Cuzzocrea. (2015) Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation . Expert Opinion on Emerging Drugs 20:4, pages 583-596.
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Rachael S Allen & Donald G Stein. (2014) Progesterone as a potential neuroprotective treatment in the retina. Expert Review of Ophthalmology 9:5, pages 375-385.
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R. Sitruk-Ware & M. El-Etr. (2013) Progesterone and related progestins: potential new health benefits. Climacteric 16:sup1, pages 69-78.
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Janet P. Niemeier, Jennifer H. Marwitz, William C. Walker, Lynne C. Davis, Tamara Bushnik, David L. Ripley & Jessica M. Ketchum. (2013) Are there cognitive and neurobehavioural correlates of hormonal neuroprotection for women after TBI?. Neuropsychological Rehabilitation 23:3, pages 363-382.
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Amy K. Wagner, Christopher A. Brett, Emily H. McCullough, Christian Niyonkuru, Tammy L. Loucks, C. Edward Dixon, Joseph Ricker, Patricia Arenth & Sarah L. Berga. (2012) Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI. Brain Injury 26:10, pages 1226-1242.
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Liliane J Dableh & James L Henry. (2011) Progesterone prevents development of neuropathic pain in a rat model: Timing and duration of treatment are critical. Journal of Pain Research 4, pages 91-101.
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Donald G. Stein. (2011) Is progesterone a worthy candidate as a novel therapy for traumatic brain injury?. Dialogues in Clinical Neuroscience 13:3, pages 352-359.
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Articles from other publishers (76)

Ayman El-Menyar, Ahammed Mekkodathil, Vishwajit Verma, Bianca M. Wahlen, Ruben Peralta, Ibrahim Taha, Suhail Hakim & Hassan Al-Thani. (2022) Gender Discrepancy in Patients with Traumatic Brain Injury: A Retrospective Study from a Level 1 Trauma Center. BioMed Research International 2022, pages 1-7.
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MPraveen Kumar, Rohit Rajput, Arti Ralta, LucindoJ Quintans-Júnior, StanleyJ C.Gutierrez, JoseMaria Barbosa-Filho, Devendra Shekhawat, BD Radotra, SK Gupta & Bikash Medhi. (2022) Evaluation of Progesterone Receptor Antagonist and Maxi-K Channel Agonist as Neuroprotective in Feeney's Weight Drop Model of TBI. Neurology India 70:4, pages 1601.
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Ida Björkgren, Sarah Mendoza, Dong Hwa Chung, Monika Haoui, Natalie True Petersen & Polina V. Lishko. (2021) The epithelial potassium channel Kir7.1 is stimulated by progesterone. Journal of General Physiology 153:10.
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Camila A. E. F. Cardinali, Yandara A. Martins & Andréa S. Torrão. (2021) Use of Hormone Therapy in Postmenopausal Women with Alzheimer’s Disease: A Systematic Review. Drugs & Aging 38:9, pages 769-791.
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Cheryl A. Frye, Vincent F. Lembo & Alicia A. Walf. (2021) Progesterone's Effects on Cognitive Performance of Male Mice Are Independent of Progestin Receptors but Relate to Increases in GABAA Activity in the Hippocampus and Cortex. Frontiers in Endocrinology 11.
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Rezvan Bazgir, Ali Siahposht-Khachaki, Esmaeil Akbari & Davood Farzin. (2021) A study of the therapeutic effects of progesterone in patients with traumatic brain injury: A systematic review and meta-analysis. Archives of Trauma Research 10:2, pages 53.
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Eitan Pe’er. 2021. Progestogens in Obstetrics and Gynecology. Progestogens in Obstetrics and Gynecology 193 202 .
Amy Gravitte, Timothy Archibald, Allison Cobble, Benjamin Kennard & Stacy Brown. (2020) Liquid chromatography–mass spectrometry applications for quantification of endogenous sex hormones. Biomedical Chromatography 35:1.
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Xiaowei Wang, Jing Tong, Xiaodi Han, Xiaoming Qi, Jun Zhang, Erxi Wu & JasonH Huang. (2020) Acute effects of human protein S administration after traumatic brain injury in mice. Neural Regeneration Research 15:11, pages 2073.
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Janet P. Niemeier. (2019) Biological Sex/Gender and Biopsychosocial Determinants of Traumatic Brain Injury Recovery Trajectories. Current Physical Medicine and Rehabilitation Reports 7:4, pages 297-304.
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Yu H. Zhong, Hong Y. Wu, Ren H. He, Bi E. Zheng & Jian Z. Fan. (2019) Sex Differences in Sex Hormone Profiles and Prediction of Consciousness Recovery After Severe Traumatic Brain Injury. Frontiers in Endocrinology 10.
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Jeff Victoroff. 2019. Concussion and Traumatic Encephalopathy. Concussion and Traumatic Encephalopathy 285 382 .
Mohammad Khaksari, Zahra Soltani & Nader Shahrokhi. (2017) Effects of Female Sex Steroids Administration on Pathophysiologic Mechanisms in Traumatic Brain Injury. Translational Stroke Research 9:4, pages 393-416.
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Machelle T. Pardue & Rachael S. Allen. (2018) Neuroprotective strategies for retinal disease. Progress in Retinal and Eye Research 65, pages 50-76.
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JoséPedro Lavrador, JoaquimCruz Teixeira, Edson Oliveira, Diogo Simão, MariaManuel Santos & Nuno Simas. (2018) Acute subdural hematoma evacuation: Predictive factors of outcome. Asian Journal of Neurosurgery 13:3, pages 565.
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Olivia J Hall & Sabra L Klein. (2017) Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites. Mucosal Immunology 10:5, pages 1097-1107.
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Jin Zhao, Quan Yuan, WeiHui Cai, Pan Sun, LiYan Ding & Fang Jin. (2016) Formulation, Optimization, Characterization, and Pharmacokinetics of Progesterone Intravenous Lipid Emulsion for Traumatic Brain Injury Therapy. AAPS PharmSciTech 18:5, pages 1475-1487.
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Mei Zhang, Jianyue Wu, Haojun Ding, Wentian Wu & Guomin Xiao. (2016) Progesterone Provides the Pleiotropic Neuroprotective Effect on Traumatic Brain Injury Through the Nrf2/ARE Signaling Pathway. Neurocritical Care 26:2, pages 292-300.
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Rene Seiger, Andreas Hahn, Allan Hummer, Georg S. Kranz, Sebastian Ganger, Michael Woletz, Christoph Kraus, Ronald Sladky, Alexander Kautzky, Siegfried Kasper, Christian Windischberger & Rupert Lanzenberger. (2016) Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration. Psychoneuroendocrinology 74, pages 371-379.
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Rachael S. Allen, Iqbal Sayeed, Yuliya Oumarbaeva, Katherine C. Morrison, Paul H. Choi, Machelle T. Pardue & Donald G. Stein. (2016) Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role. Restorative Neurology and Neuroscience 34:6, pages 947-963.
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Xin-Yu Lu, Hui Sun, Qiao-Yu Li & Pei-Song Lu. (2016) Progesterone for Traumatic Brain Injury: A Meta-Analysis Review of Randomized Controlled Trials. World Neurosurgery 90, pages 199-210.
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Muhammad Shafiq, Youngmee Jung & Soo Hyun Kim. (2016) Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair. Biomaterials 90, pages 85-115.
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Rastafa I. Geddes, Bethany L. Peterson, Donald G. Stein & Iqbal Sayeed. (2016) Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury. PLOS ONE 11:1, pages e0146419.
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Kyria M. Webster, David K. Wright, Mujun Sun, Bridgette D. Semple, Ezgi Ozturk, Donald G. Stein, Terence J. O’Brien & Sandy R. Shultz. (2015) Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury. Journal of Neuroinflammation 12:1.
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Yunhui Zeng, Yujie Zhang, Junpeng Ma & Jianguo Xu. (2015) Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials. PLOS ONE 10:10, pages e0140624.
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Stanley Jacob & Jack de la Torre. 2015. Dimethyl Sulfoxide (DMSO) in Trauma and Disease. Dimethyl Sulfoxide (DMSO) in Trauma and Disease 203 240 .
Courtney L. Robertson, Emin Fidan, Rachel M. Stanley, Corina Noje & Hülya Bayir. (2015) Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury. Pediatric Critical Care Medicine 16:3, pages 236-244.
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Pardes Habib & Cordian Beyer. (2015) Regulation of brain microglia by female gonadal steroids. The Journal of Steroid Biochemistry and Molecular Biology 146, pages 3-14.
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David J. Loane, Bogdan A. Stoica & Alan I. Faden. 2015. Traumatic Brain Injury, Part I. Traumatic Brain Injury, Part I 343 366 .
Eitan Pe’er. 2015. Progestogens in Obstetrics and Gynecology. Progestogens in Obstetrics and Gynecology 177 182 .
David W. Wright, Sharon D. Yeatts, Robert Silbergleit, Yuko Y. Palesch, Vicki S. Hertzberg, Michael Frankel, Felicia C. Goldstein, Angela F. Caveney, Harriet Howlett-Smith, Erin M. Bengelink, Geoffrey T. Manley, Lisa H. Merck, L. Scott Janis & William G. Barsan. (2014) Very Early Administration of Progesterone for Acute Traumatic Brain Injury. New England Journal of Medicine 371:26, pages 2457-2466.
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James Crownover & Amy Wagner. 2014. Biomarkers of Brain Injury and Neurological Disorders. Biomarkers of Brain Injury and Neurological Disorders 236 273 .
Janet P. NiemeierPaul B. PerrinMegan G. HolcombCynthia D. RolstonLaura K. ArtmanJuan LuKarine S. Nersessova. (2014) Gender Differences in Awareness and Outcomes During Acute Traumatic Brain Injury Recovery. Journal of Women's Health 23:7, pages 573-580.
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Martina SantarsieriChristian NiyonkuruEmily H. McCulloughJulie A. DobosC. Edward DixonSarah L. BergaAmy K. Wagner. (2014) Cerebrospinal Fluid Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe Traumatic Brain Injury. Journal of Neurotrauma 31:8, pages 699-712.
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Anusha Jayaraman & Christian J. Pike. (2014) Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons. Molecular and Cellular Endocrinology 384:1-2, pages 52-60.
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Ethika Tyagi, Rahul Agrawal, Zhe Ying & Fernando Gomez-Pinilla. (2014) TBI and sex: Crucial role of progesterone protecting the brain in an omega−3 deficient condition. Experimental Neurology 253, pages 41-51.
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M.F. Coronel, F. Labombarda, A.F. De Nicola & S.L. González. (2014) Progesterone reduces the expression of spinal cyclooxygenase-2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain. European Journal of Pain 18:3, pages 348-359.
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Valentina Vacca, Sara Marinelli, Luisa Pieroni, Andrea Urbani, Siro Luvisetto & Flaminia Pavone. (2014) Higher pain perception and lack of recovery from neuropathic pain in females: A behavioural, immunohistochemical, and proteomic investigation on sex-related differences in mice. Pain 155:2, pages 388-402.
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Rastafa I. Geddes, Eric A. Sribnick, Iqbal Sayeed & Donald G. Stein. (2014) Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury. PLoS ONE 9:1, pages e87252.
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Shruti Kabadi & Alan Faden. (2014) Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation. International Journal of Molecular Sciences 15:1, pages 1216-1236.
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Matthew Birnie, Ryan Morrison, Ramatoulie Camara & Kenneth I Strauss. (2013) Temporal changes of cytochrome P450 (Cyp) and eicosanoid-related gene expression in the rat brain after traumatic brain injury. BMC Genomics 14:1.
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Jing Wei & Guo-min Xiao. (2013) The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects. Acta Pharmacologica Sinica 34:12, pages 1485-1490.
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Jung-Chun Lin, Te-Jung Liu, Shih-Wei Hsu, Kuan-Yin Tseng, Tung-Han Tsai, Hsin-I Ma & Dueng-Yuan Hueng. (2013) Letter to the Editor: Closed head injury. Journal of Neurosurgery 119:5, pages 1349-1350.
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Ka Chun Un, Yue Chun Wang, Wutian Wu & Gilberto Ka Kit Leung. (2013) Systemic progesterone for modulating electrocautery-induced secondary brain injury. Journal of Clinical Neuroscience 20:9, pages 1329-1330.
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Emily R. Rosario, Melissa R. Bustos & Colleen Moore. (2013) Hypothalamic pituitary dysfunction following traumatic brain injury. Social Care and Neurodisability 4:3/4, pages 134-146.
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Frank Z. StanczykJanet P. Hapgood, Sharon Winer & Daniel R. MishellJr.Jr.. (2013) Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects. Endocrine Reviews 34:2, pages 171-208.
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Ye Xiong, Asim Mahmood & Michael Chopp. (2013) Animal models of traumatic brain injury. Nature Reviews Neuroscience 14:2, pages 128-142.
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Rodney M. Ritzel, Lori A. Capozzi & Louise D. McCullough. (2013) Sex, stroke, and inflammation: The potential for estrogen-mediated immunoprotection in stroke. Hormones and Behavior 63:2, pages 238-253.
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María Angeles Arevalo, María Santos-Galindo, Estefanía Acaz-Fonseca, Iñigo Azcoitia & Luis M. Garcia-Segura. (2013) Gonadal hormones and the control of reactive gliosis. Hormones and Behavior 63:2, pages 216-221.
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Amy K. Wagner & Kevin T. Zitelli. (2013) A Rehabilomics focused perspective on molecular mechanisms underlying neurological injury, complications, and recovery after severe TBI. Pathophysiology 20:1, pages 39-48.
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D. Meffre, F. Labombarda, B. Delespierre, A. Chastre, A.F. De Nicola, D.G. Stein, M. Schumacher & R. Guennoun. (2013) Distribution of membrane progesterone receptor alpha in the male mouse and rat brain and its regulation after traumatic brain injury. Neuroscience 231, pages 111-124.
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Todd C. PetersonGail D. AndersonEric D. KantorMichael R. Hoane. (2012) A Comparison of the Effects of Nicotinamide and Progesterone on Functional Recovery of Cognitive Behavior following Cortical Contusion Injury in the Rat. Journal of Neurotrauma 29:18, pages 2823-2830.
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Alok Kumar & David J. Loane. (2012) Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention. Brain, Behavior, and Immunity 26:8, pages 1191-1201.
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Ye Xiong, Asim Mahmood, Yuling Meng, Yanlu Zhang, Zheng Gang Zhang, Daniel C. Morris & Michael Chopp. (2012) Neuroprotective and neurorestorative effects of thymosin β4 treatment following experimental traumatic brain injury. Annals of the New York Academy of Sciences 1270:1, pages 51-58.
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Chang Su, Rebecca L. Cunningham, Nataliya Rybalchenko & Meharvan Singh. (2012) Progesterone Increases the Release of Brain-Derived Neurotrophic Factor from Glia via Progesterone Receptor Membrane Component 1 (Pgrmc1)-Dependent ERK5 Signaling. Endocrinology 153:9, pages 4389-4400.
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Xiaowei Li, Eleni Katsanevakis, Xiaoyan Liu, Ning Zhang & Xuejun Wen. (2012) Engineering neural stem cell fates with hydrogel design for central nervous system regeneration. Progress in Polymer Science 37:8, pages 1105-1129.
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Aruni S. Arachchige Don, Chi Kwan Tsang, Tatiana M. Kazdoba, Gabriella D?Arcangelo, Wise Young & X.F. Steven Zheng. (2012) Targeting mTOR as a novel therapeutic strategy for traumatic CNS injuries. Drug Discovery Today 17:15-16, pages 861-868.
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Shilpa N Kaore, Deepak Kumar Langade, Vijay Kumar Yadav, Parag Sharma, Vijay R Thawani & Raj Sharma. (2012) Novel actions of progesterone: what we know today and what will be the scenario in the future?. Journal of Pharmacy and Pharmacology 64:8, pages 1040-1062.
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David B. Guthrie, Donald G. Stein, Dennis C. Liotta, Mark A. Lockwood, Iqbal Sayeed, Fahim Atif, Richard F. Arrendale, G. Prabhakar Reddy, Taylor J. Evers, Jose R. Marengo, Randy B. Howard, Deborah G. Culver & Michael G. Natchus. (2012) Water-Soluble Progesterone Analogues Are Effective, Injectable Treatments in Animal Models of Traumatic Brain Injury. ACS Medicinal Chemistry Letters 3:5, pages 362-366.
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Fang Hua, Jenny I. Reiss, Huiling Tang, Jun Wang, Xavier Fowler, Iqbal Sayeed & Donald G. Stein. (2012) Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury. Hormones and Behavior 61:4, pages 642-651.
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Ha Na Kim, Sook-Jeong Lee & Jae-Young Koh. (2012) The neurosteroids, allopregnanolone and progesterone, induce autophagy in cultured astrocytes. Neurochemistry International 60:2, pages 125-133.
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María Santos-Galindo, Estefanía Acaz-Fonseca, María J Bellini & Luis M Garcia-Segura. (2011) Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biology of Sex Differences 2:1.
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Iñigo Azcoitia, Maria-Angeles Arevalo, Alejandro F. De Nicola & Luis M. Garcia-Segura. (2011) Neuroprotective actions of estradiol revisited. Trends in Endocrinology & Metabolism 22:12, pages 467-473.
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Tamara R. Espinoza & David W. Wright. (2011) The Role of Progesterone in Traumatic Brain Injury. Journal of Head Trauma Rehabilitation 26:6, pages 497-499.
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Rashad Hussain, Martine El-Etr, Ouardia Gaci, Jennifer Rakotomamonjy, Wendy B. Macklin, Narender Kumar, Regine Sitruk-Ware, Michael Schumacher & Abdel M. Ghoumari. (2011) Progesterone and Nestorone Facilitate Axon Remyelination: A Role for Progesterone Receptors. Endocrinology 152:10, pages 3820-3831.
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Bruce Ryan Bistrian, Wayne Askew, John W. ErdmanJrJr & Maria P. Oria. (2011) Nutrition and Traumatic Brain Injury. Journal of Parenteral and Enteral Nutrition 35:5, pages 556-559.
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Gail D. AndersonFederico M. FarinTheo K. BammlerRichard P. BeyerAlicia A. SwanHui-Wen WilkersonEric D. KantorMichael R. Hoane. (2011) The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury. Journal of Neurotrauma 28:9, pages 1827-1843.
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Florencia Labombarda, Susana González, Analia Lima, Paulina Roig, Rachida Guennoun, Michael Schumacher & Alejandro F. De Nicola. (2011) Progesterone attenuates astro- and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury. Experimental Neurology 231:1, pages 135-146.
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Cindy K. Barha, Tauheed Ishrat, Jonathan R. Epp, Liisa A.M. Galea & Donald G. Stein. (2011) Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. Experimental Neurology 231:1, pages 72-81.
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María Florencia Coronel, Florencia Labombarda, Paulina Roig, Marcelo José Villar, Alejandro Federico De Nicola & Susana Laura González. (2011) Progesterone Prevents Nerve Injury-Induced Allodynia and Spinal NMDA Receptor Upregulation in Rats. Pain Medicine 12:8, pages 1249-1261.
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V. Ramana Feeser & Roger M. Loria. (2011) Modulation of traumatic brain injury using progesterone and the role of glial cells on its neuroprotective actions. Journal of Neuroimmunology 237:1-2, pages 4-12.
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. (2011) Current World Literature. Current Opinion in Anaesthesiology 24:2, pages 224-233.
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Cheryl A. Frye & Alicia Walf. (2011) Progesterone, administered before kainic acid, prevents decrements in cognitive performance in the Morris Water Maze. Developmental Neurobiology 71:2, pages 142-152.
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Fang Hua, Jun Wang, Tauheed Ishrat, Wenjing Wei, Fahim Atif, Iqbal Sayeed & Donald G Stein. (2011) Genomic profile of Toll-like receptor pathways in traumatically brain-injured mice: effect of exogenous progesterone. Journal of Neuroinflammation 8:1, pages 42.
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David J. Loane & Alan I. Faden. (2010) Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends in Pharmacological Sciences 31:12, pages 596-604.
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Tauheed Ishrat, Iqbal Sayeed, Fahim Atif, Fang Hua & Donald G. Stein. (2010) Progesterone and allopregnanolone attenuate blood–brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases. Experimental Neurology 226:1, pages 183-190.
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