{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:08Z","timestamp":1787027828491,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The enteric nervous system (ENS) is an intrinsic network of neuronal ganglia in the intestinal tube with about 100 million neurons located in the myenteric plexus and submucosal plexus. These neurons being affected in neurodegenerative diseases, such as Parkinson\u2019s disease, before pathological changes in the central nervous system (CNS) become detectable is currently a subject of discussion. Understanding how to protect these neurons is, therefore, particularly important. Since it has already been shown that the neurosteroid progesterone mediates neuroprotective effects in the CNS and PNS, it is now equally important to see whether progesterone has similar effects in the ENS. For this purpose, the RT-qPCR analyses of laser microdissected ENS neurons were performed, showing for the first time the expression of the different progesterone receptors (PR-A\/B; mPRa, mPRb, PGRMC1) in rats at different developmental stages. This was also confirmed in ENS ganglia using immunofluorescence techniques and confocal laser scanning microscopy. To analyze the potential neuroprotective effects of progesterone in the ENS, we stressed dissociated ENS cells with rotenone to induce damage typical of Parkinson\u2019s disease. The potential neuroprotective effects of progesterone were then analyzed in this system. Treatment of cultured ENS neurons with progesterone reduced cell death by 45%, underscoring the tremendous neuroprotective potential of progesterone in the ENS. The additional administration of the PGRMC1 antagonist AG205 abolished the observed effect, indicating the crucial role of PGRMC1 with regard to the neuroprotective effect of progesterone.<\/jats:p>","DOI":"10.3390\/cells12081206","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T06:06:18Z","timestamp":1682057178000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Progesterone: A Neuroprotective Steroid of the Intestine"],"prefix":"10.3390","volume":"12","author":[{"given":"Lennart Norman","family":"Stegemann","sequence":"first","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Maria","family":"Neufeld","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Hecking","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4642","authenticated-orcid":false,"given":"Matthias","family":"Vorgerd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, D-44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-4485","authenticated-orcid":false,"given":"Veronika","family":"Matschke","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Stahlke","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-0143","authenticated-orcid":false,"given":"Carsten","family":"Theiss","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, D-44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/ar.24121","article-title":"Progesterone Effects in the Nervous System","volume":"302","author":"Theis","year":"2019","journal-title":"Anat. Rec."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.bbcan.2016.07.004","article-title":"The Emerging Role of Progesterone Receptor Membrane Component 1 (PGRMC1) in Cancer Biology","volume":"1866","author":"Cahill","year":"2016","journal-title":"Biochim. Et Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0960-0760(90)90490-C","article-title":"Neurosteroids: A New Brain Function?","volume":"37","author":"Baulieu","year":"1990","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pneurobio.2010.04.009","article-title":"Progress in Dorsal Root Ganglion Neurosteroidogenic Activity: Basic Evidence and Pathophysiological Correlation","volume":"92","author":"Schaeffer","year":"2010","journal-title":"Prog. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1007\/s00018-013-1448-4","article-title":"Long-Term Incubation with Mifepristone (MLTI) Increases the Spine Density in Developing Purkinje Cells: New Insights into Progesterone Receptor Mechanisms","volume":"71","author":"Wessel","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.yhbeh.2012.06.003","article-title":"Progesterone and Neuroprotection","volume":"63","author":"Singh","year":"2013","journal-title":"Horm. Behav."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12782","DOI":"10.1111\/jne.12782","article-title":"Neuroprotection and Immunomodulation of Progesterone in the Gut of a Mouse Model of Parkinson\u2019s Disease","volume":"32","author":"Jarras","year":"2020","journal-title":"J. Neuroendocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0165-1838(00)00127-2","article-title":"Types of Neurons in the Enteric Nervous System","volume":"81","author":"Furness","year":"2000","journal-title":"J. Auton. Nerv. Syst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1212\/WNL.0b013e318236ef60","article-title":"Parkinson Disease: The Enteric Nervous System Spills Its Guts","volume":"77","author":"Derkinderen","year":"2011","journal-title":"Neurology"},{"key":"ref_10","first-page":"203","article-title":"The Gut-Brain Axis: Interactions between Enteric Microbiota, Central and Enteric Nervous Systems","volume":"28","author":"Carabotti","year":"2015","journal-title":"Ann. Gastroenterol. Q. Publ. Hell. Soc. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nrgastro.2009.35","article-title":"Principles and Clinical Implications of the Brain\u2013Gut\u2013Enteric Microbiota Axis","volume":"6","author":"Rhee","year":"2009","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","article-title":"Gastric \u03b1-Synuclein Immunoreactive Inclusions in Meissner\u2019s and Auerbach\u2019s Plexuses in Cases Staged for Parkinson\u2019s Disease-Related Brain Pathology","volume":"396","author":"Braak","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00401-014-1343-6","article-title":"Direct Evidence of Parkinson Pathology Spread from the Gastrointestinal Tract to the Brain in Rats","volume":"128","author":"Holmqvist","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S0140-6736(95)92707-7","article-title":"Dopaminergic Defect of Enteric Nervous System in Parkinson\u2019s Disease Patients with Chronic Constipation","volume":"346","author":"Singaram","year":"1995","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chia, S.J., Tan, E.-K., and Chao, Y.-X. (2020). Historical Perspective: Models of Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072464"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1111\/j.1471-4159.2006.04333.x","article-title":"Mechanism of Toxicity in Rotenone Models of Parkinson\u2019s Disease","volume":"100","author":"Sherer","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.3389\/fnins.2019.01028","article-title":"The Impairments of \u03b1-Synuclein and Mechanistic Target of Rapamycin in Rotenone-Induced SH-SY5Y Cells and Mice Model of Parkinson\u2019s Disease","volume":"13","author":"Ramalingam","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10571-021-01181-5","article-title":"Methods to Study the Myenteric Plexus of Rat Small Intestine","volume":"43","author":"Hecking","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1177\/02841851960373P296","article-title":"Toxicity of Ethanol in Low Concentrations: Experimental Evaluation in Cell Culture","volume":"37","author":"Tapani","year":"1996","journal-title":"Acta Radiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"G493","DOI":"10.1152\/ajpgi.90214.2008","article-title":"Overexpression of Progesterone Receptor B Increases Sensitivity of Human Colon Muscle Cells to Progesterone","volume":"295","author":"Cheng","year":"2008","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.yfrne.2008.02.001","article-title":"Progesterone Receptors: Form and Function in Brain","volume":"29","author":"Brinton","year":"2008","journal-title":"Front. Neuroendocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1006\/hbeh.1994.1043","article-title":"Gene Expression of Progesterone Receptor Isoforms in the Rat Brain","volume":"28","author":"Kato","year":"1994","journal-title":"Horm. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0006-8993(99)01424-9","article-title":"Expression of Intracellular Progesterone Receptors in Rat Brain during Different Reproductive States, and Involvement in Maternal Behavior","volume":"830","author":"Numan","year":"1999","journal-title":"Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mce.2011.09.016","article-title":"Progesterone Receptors, Their Isoforms and Progesterone Regulated Transcription","volume":"357","author":"Jacobsen","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0361-9230(00)00410-X","article-title":"Progesterone Receptor Isoforms Expression in the Prepuberal and Adult Male Rat Brain","volume":"54","author":"Salazar","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0304-3940(03)00362-8","article-title":"Neonatal Expression of Progesterone Receptor Isoforms in the Cerebellar Purkinje Cell in Rats","volume":"343","author":"Sakamoto","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"547","DOI":"10.4103\/1673-5374.155417","article-title":"Progesterone: A Universal Stimulus for Neuronal Cells?","volume":"10","author":"Theis","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mce.2014.07.022","article-title":"Progesterone Receptor Expression in Granulosa Cells Is Suppressed by MicroRNA-378-3p","volume":"399","author":"Toms","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0039-128X(00)00112-4","article-title":"Progesterone Receptor Coactivators","volume":"65","author":"Rowan","year":"2000","journal-title":"Steroids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1210\/en.2012-1469","article-title":"Distribution and Estrogen Regulation of Membrane Progesterone Receptor-\u03b2 in the Female Rat Brain","volume":"153","author":"Zuloaga","year":"2012","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.neuroscience.2010.10.051","article-title":"Distribution of MRNAs Encoding Classical Progestin Receptor, Progesterone Membrane Components 1 and 2, Serpine MRNA Binding Protein 1, and Progestin and ADIPOQ Receptor Family Members 7 and 8 in Rat Forebrain","volume":"172","author":"Intlekofer","year":"2011","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1046\/j.1471-4159.2003.02055.x","article-title":"Effects of Injury and Progesterone Treatment on Progesterone Receptor and Progesterone Binding Protein 25-Dx Expression in the Rat Spinal Cord","volume":"87","author":"Labombarda","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.neuroscience.2012.11.039","article-title":"Distribution of Membrane Progesterone Receptor Alpha in the Male Mouse and Rat Brain and Its Regulation after Traumatic Brain Injury","volume":"231","author":"Meffre","year":"2013","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/srep00898","article-title":"Environmental Toxins Trigger PD-like Progression via Increased Alpha-Synuclein Release from Enteric Neurons in Mice","volume":"2","author":"Schwarz","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pan-Montojo, F., Anichtchik, O., Dening, Y., Knells, L., Pursche, S., Jung, R., Jackson, S., Gille, G., Spillantini, M.G., and Reichmann, H. (2010). Progression of Parkinson\u2019s Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice. PLoS ONE, 5.","DOI":"10.1038\/npre.2010.3352.3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.mce.2010.02.005","article-title":"Progesterone Inhibits Apoptosis in Part by PGRMC1-Regulated Gene Expression","volume":"320","author":"Peluso","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1177\/0271678X18793324","article-title":"Sex Differences in Stroke: Challenges and Opportunities","volume":"38","author":"Bushnell","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41582-018-0091-y","article-title":"Traumatic Brain Injury: Sex, Gender and Intersecting Vulnerabilities","volume":"14","author":"Mollayeva","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3233\/JPD-191683","article-title":"Parkinson\u2019s Disease in Women and Men: What\u2019s the Difference?","volume":"9","author":"Cerri","year":"2019","journal-title":"J. Parkinson\u2019S Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1210\/en.2007-1050","article-title":"Progesterone Receptor Membrane Component-1 (PGRMC1) Is the Mediator of Progesterone\u2019s Antiapoptotic Action in Spontaneously Immortalized Granulosa Cells as Revealed by PGRMC1 Small Interfering Ribonucleic Acid Treatment and Functional Analysis of PGRMC1 Mutations","volume":"149","author":"Peluso","year":"2008","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1095\/biolreprod.105.041061","article-title":"Expression and Function of PAIRBP1 within Gonadotropin-Primed Immature Rat Ovaries: PAIRBP1 Regulation of Granulosa and Luteal Cell Viability","volume":"73","author":"Peluso","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1095\/biolreprod.112.103036","article-title":"Plasminogen Activator Inhibitor 1 RNA-Binding Protein Interacts with Progesterone Receptor Membrane Component 1 to Regulate Progesterone\u2019s Ability to Maintain the Viability of Spontaneously Immortalized Granulosa Cells and Rat Granulosa Cells","volume":"88","author":"Peluso","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jsbmb.2007.02.002","article-title":"Progesterone Receptor Membrane Component 1: An Integrative Review","volume":"105","author":"Cahill","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.mce.2011.07.017","article-title":"Structural and Functional Analysis of Domains of the Progesterone Receptor","volume":"348","author":"Hill","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"T1","DOI":"10.1530\/JME-19-0212","article-title":"New Insights into Progesterone Receptor Signaling in the Endometrium Required for Embryo Implantation","volume":"65","author":"DeMayo","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1073\/pnas.67.2.501","article-title":"Progesterone \u201cReceptors\u201d in the Cytoplasm and Nucleus of Chick Oviduct Target Tissue","volume":"67","author":"Sherman","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MN:34:3:249","article-title":"Phosphoinositide-3-Kinase\/Akt Survival Signal Pathways Are Implicated in Neuronal Survival after Stroke","volume":"34","author":"Zhao","year":"2006","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.neuroscience.2012.03.008","article-title":"Progesterone Is Neuroprotective against Ischemic Brain Injury through Its Effects on the Phosphoinositide 3-Kinase\/Protein Kinase B Signaling Pathway","volume":"210","author":"Ishrat","year":"2012","journal-title":"Neuroscience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000511207","article-title":"Suppression of NLRP3 Inflammasome, Pyroptosis, and Cell Death by NIM811 in Rotenone-Exposed Cells as an in Vitro Model of Parkinson\u2019s Disease","volume":"20","author":"Zhang","year":"2020","journal-title":"Neurodegener. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1385\/ENDO:14:3:407","article-title":"Ovarian Hormones Elicit Phosphorylation of Akt and Extracellular-Signal Regulated Kinase in Explants of the Cerebral Cortex","volume":"14","author":"Singh","year":"2001","journal-title":"Endocrine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/jne.12060","article-title":"Nonclassical Progesterone Signalling Molecules in the Nervous System","volume":"25","author":"Petersen","year":"2013","journal-title":"J. Neuroendocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.neuint.2006.02.003","article-title":"Rotenone Induces Cell Death in Primary Dopaminergic Culture by Increasing ROS Production and Inhibiting Mitochondrial Respiration","volume":"49","author":"Radad","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/81834","article-title":"Chronic Systemic Pesticide Exposure Reproduces Features of Parkinson\u2019s Disease","volume":"3","author":"Betarbet","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02815156","article-title":"Progesterone Protects against Lipid Peroxidation Following Traumatic Brain Injury in Rats","volume":"31","author":"Roof","year":"1997","journal-title":"Mol. Chem. Neuropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000086485","article-title":"Overexpression of the Cytochrome P450 Activator Hpr6 (Heme-1 Domain Protein\/Human Progesterone Receptor) in Tumors","volume":"26","author":"Crudden","year":"2005","journal-title":"Tumor Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/jcb.10648","article-title":"Hpr6. 6 Protein Mediates Cell Death from Oxidative Damage in MCF-7 Human Breast Cancer Cells","volume":"90","author":"Hand","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Guennoun, R. (2020). Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155271"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.annemergmed.2006.07.932","article-title":"ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury","volume":"49","author":"Wright","year":"2007","journal-title":"Ann. Emerg. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"R61","DOI":"10.1186\/cc6887","article-title":"Improved Outcomes from the Administration of Progesterone for Patients with Acute Severe Traumatic Brain Injury: A Randomized Controlled Trial","volume":"12","author":"Xiao","year":"2008","journal-title":"Crit. Care"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa1404304","article-title":"Very Early Administration of Progesterone for Acute Traumatic Brain Injury","volume":"371","author":"Wright","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMoa1411090","article-title":"A Clinical Trial of Progesterone for Severe Traumatic Brain Injury","volume":"371","author":"Skolnick","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1089\/neu.2021.0064","article-title":"Response to Korley et al.: Progesterone Treatment Does Not Decrease Serum Levels of Biomarkers of Glial and Neuronal Cell Injury in Moderate and Severe TBI Subjects: A Secondary Analysis of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III Trial (DOI: 10.1089\/Neu. 2020.7072)","volume":"38","author":"Sayeed","year":"2021","journal-title":"J. Neurotrauma"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:36Z","timestamp":1760124036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":63,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cells12081206"],"URL":"https:\/\/doi.org\/10.3390\/cells12081206","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}