title: The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats.
abstract: This report compares the effects of progesterone and its metabolite, allopregnanolone, on the early injury cascade (apoptosis) and long-term functional deficits after TBI. Progesterone (16 mg/kg) or allopregnanolone (4, 8, or 16 mg/kg) were injected at 1 h, 6 h, and then for 5 consecutive days after bilateral contusions of the frontal cortex in adult male rats. Within one day after injury, progesterone and allopregnanolone reduced both the expression of pro-apoptotic proteins caspase-3 and Bax, and apoptotic DNA fragmentation. Progesterone and allopregnanolone also reduced the size of glial fibrillary acid protein (GFAP)-positive astrocytes at the lesion site 24 h after injury. Compared to sham-operated controls at 19 days after injury, injured rats given either progesterone or any of three doses of allopregnanolone had equivalent numbers of ChAT-positive cells in the nucleus basalis magnocellularis. At 19 days post-injury, rats given progesterone or allopregnanolone (8 mg/kg) showed improved performance in a spatial learning task compared to injured rats given only the vehicle. These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone and allopregnanolone and help to explain why better cognitive performance is observed after injury when animals are given either neurosteroid.
authors.affiliation: Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Djebaili
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Guo
authors.forename: Edward H
authors.initials: EH
authors.lastname: Pettus
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Hoffman
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011374:Progesterone; D011280:Pregnanolone; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases