ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- A Pilot Systematic Review and Meta-analysis of Neuroprotective Studies in Female Rodent Models of Ischemic Stroke.Translational stroke research · 2024Pooled it
- p-Coumaric acid alleviates neuronal damage in ischemic stroke mice by promoting BACH1 nuclear export and degradation.Acta pharmacologica Sinica · 2025Article
- Estradiol Promotes Myelin Repair in the Spinal Cord of Female Mice in a CXCR4 Chemokine Receptor-Independent Manner.International journal of molecular sciences · 2025Article
- Estrogen and progesterone attenuate CD4-positive immune cell traffic to the penumbra region of rat's ischemic stroke brain.Iranian journal of basic medical sciences · 2025Article
- Mild TBI Changes Brain and Plasma Neurosteroid Levels in Mice.Neurotrauma reports · 2025Article
- β-elemene promotes microglial M2-like polarization against ischemic stroke via AKT/mTOR signaling axis-mediated autophagy.Chinese medicine · 2024Article
- Novel metabolic biomarkers for the diagnosis of acute ischemic stroke.Biomarkers in medicine · 2024Article
- Low glycemic index diet restrains epileptogenesis in a gender-specific fashion.Cellular and molecular life sciences : CMLS · 2023Article
- Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway.Brain and behavior · 2023Article
- Chronic administration of XBD173 ameliorates cognitive deficits and neuropathology via 18 kDa translocator protein (TSPO) in a mouse model of Alzheimer's disease.Translational psychiatry · 2023Article
- Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Strontium Attenuates Hippocampal Damage via Suppressing Neuroinflammation in High-Fat Diet-Induced NAFLD Mice.International journal of molecular sciences · 2023Article
- Membrane Progesterone Receptors (mPRs/PAQRs) Are Going beyond Its Initial Definitions.Membranes · 2023Review
- Limbic progesterone receptors regulate spatial memory.Scientific reports · 2023Article
- The Comprehensive Steroidome in Complete TSPO/PBR Knockout Mice under Basal Conditions.International journal of molecular sciences · 2023Article
- Immune regulation based on sex differences in ischemic stroke pathology.Frontiers in immunology · 2023Review
- Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.Journal of neuroendocrinology · 2022Review
- Combination therapy for cerebral ischemia: do progesterone and noscapine provide better neuroprotection than either alone in the treatment?Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.