title: Progesterone for neuroprotection in pediatric traumatic brain injury.
abstract: 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.
  
  
  METHODS
  National Library of Medicine PubMed literature review.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
authors.affiliation: 1Department 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.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Robertson
authors.forename: Emin
authors.initials: E
authors.lastname: Fidan
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Stanley
authors.forename: Corina
authors.initials: C
authors.lastname: Noje
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D011372:Progestins; D011374:Progesterone