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Updated: Apr 18, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Progesterone for neuroprotection in pediatric traumatic brain injury
Courtney L Robertson1, Emin Fidan, Rachel M Stanley
11Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 2Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD. 3Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA. 4Departments of Emergency Medicine and Pediatrics, University of Michigan, Ann Arbor, MI. 5Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA.
Insights
Progesterone shows neuroprotective effects in adult traumatic brain injury models. Further research in pediatric models is needed to explore its potential for treating head injuries in children.
Area of Science:
- Neuroscience
- Pharmacology
- Pediatric Traumatology
Background:
- Progesterone exhibits neuroprotective properties by mitigating secondary injury cascades like cerebral edema and neuroinflammation.
- Extensive preclinical data exists for progesterone in adult traumatic brain injury (TBI) models, with ongoing clinical trials.
Purpose of the Study:
- To review preclinical evidence of progesterone's neuroprotective effects in traumatic brain injury (TBI).
- To examine unique aspects of the developing brain relevant to progesterone's efficacy in pediatric TBI.
- To assess the current status of clinical trials for progesterone in adult TBI.
Main Methods:
- Comprehensive literature review of preclinical studies on progesterone and TBI using PubMed.
- Analysis of progesterone's mechanisms of neuroprotection.
- Evaluation of unique developmental brain injury features.
Main Results:
- Over 40 adult animal studies support progesterone's neuroprotective role in TBI.
- Limited preclinical research exists for progesterone in pediatric brain injury models.
- Two Phase II and ongoing Phase III clinical trials are evaluating progesterone for adult TBI.
Conclusions:
- The developing brain's distinct characteristics necessitate independent study of progesterone in immature TBI models.
- Further preclinical research may enable a new neuroprotective therapy for pediatric TBI.
- Progesterone could potentially benefit other pediatric brain injuries like ischemia, stroke, and status epilepticus.
Objective:
To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury.
Data Sources:
National Library of Medicine PubMed literature review.
Study Selection:
The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult traumatic brain injury is reviewed.
Data Extraction And Data Synthesis:
Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human phase II trials of progesterone for adult traumatic brain injury have been published, and two multicenter phase III trials are underway.
Conclusions:
The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of traumatic brain injury. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, and statue epilepticus).
