ArticleFrontiers in neuroscience2013
Therapeutic effects of progesterone and its metabolites in traumatic brain injury may involve non-classical signaling mechanisms.
Article in Frontiers in neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Advances and challenges in experimental models of posttraumatic epilepsy for therapeutic interventions.Pharmacological reviews · 2025Review
- Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials.Biomedicines · 2022Review
- New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling.American journal of cancer research · 2021Review
- A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits.Frontiers in pharmacology · 2021Article
- Genomic and Non-genomic Action of Neurosteroids in the Peripheral Nervous System.Frontiers in neuroscience · 2020Review
- Anti-apoptotic Actions of Allopregnanolone and Ganaxolone Mediated Through Membrane Progesterone Receptors (PAQRs) in Neuronal Cells.Frontiers in endocrinology · 2020Review
- Steroid Hormones and Their Action in Women's Brains: The Importance of Hormonal Balance.Frontiers in public health · 2018Review
- Progesterone-mediated angiogenic activity of endothelial progenitor cell and angiogenesis in traumatic brain injury rats were antagonized by progesterone receptor antagonist.Cell proliferation · 2017Article
- The Neurosteroidogenic Enzyme 5α-Reductase Mediates Psychotic-Like Complications of Sleep Deprivation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Schwann cell development, maturation and regeneration: a focus on classic and emerging intracellular signaling pathways.Neural regeneration research · 2017Review
- Allopregnanolone mediates the exacerbation of Tourette-like responses by acute stress in mouse models.Scientific reports · 2017Article
- Inhibitory respiratory responses to progesterone and allopregnanolone in newborn rats chronically treated with caffeine.The Journal of physiology · 2016Article
- Neurosteroids Involvement in the Epigenetic Control of Memory Formation and Storage.Neural plasticity · 2016Review
- Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?Reviews in endocrine & metabolic disorders · 2015Review
- Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124.Pharmacology, biochemistry, and behavior · 2014Article
- Cerebrospinal fluid cortisol and progesterone profiles and outcomes prognostication after severe traumatic brain injury.Journal of neurotrauma · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Traumatic brain injury (TBI) is an important and costly medical problem for which no clinically proven treatment currently exists. Studies in rodents and humans have shown beneficial effects of progesterone (P4) on both mortality and functional outcomes following TBI. Neuroprotective effects of P4 in TBI likely involve the classical nuclear progesterone receptors (Pgr) that are widely distributed in both glial cells and neurons of the brain. However, P4 may have critical effects not mediated through Pgr. In the brain, P4 is converted to a metabolite, allopregnanolone (ALLO), whose beneficial effects equal or exceed those of P4 in TBI. ALLO does not bind Pgr, suggesting it acts through non-classical pathways. ALLO has effects on GABAA and pregnane X receptors, as well as on the mitochondrial permeability transition pore. In addition, ALLO is metabolized to another compound, 5alpha-dihydroprogesterone, which binds Pgr, suggesting ALLO actions may involve signaling through Pgr as well as the aforementioned mechanisms of action. P4 and ALLO also signal through a number of membrane receptors (progesterone receptor membrane component 1, and membrane progesterone receptors (mPRs) alpha, beta, gamma, delta, and epsilon) in the brain that are distinct from Pgr, although the role of these receptors in the normal brain and in the therapeutic response to P4 and ALLO following TBI is unclear. In summary, P4 has the potential to become the first clinically effective treatment for TBI, and the effects of P4 and its metabolite ALLO in TBI may involve Pgr, mPRs, and other signaling pathways. Elucidating these mechanisms will more clearly reveal the potential of classical and non-classical pathways to mediate important effects of P4 and its metabolites, and potentially offer new therapeutic approaches to TBI.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.