title: Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?
abstract: There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neuroprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inflammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphorylation of Akt via its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvested at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a significant decrease in Akt phosphorylation compared to sham operation. However, mice treated with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our findings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Richard Justin
authors.initials: RJ
authors.lastname: Garling
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA ; Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA ; Department of Neurology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Lora Talley
authors.initials: LT
authors.lastname: Watts
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Sprague
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Fletcher
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Jimenez
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Digicaylioglu
keywords: Akt; apoptosis; brain injury; controlled cortical impact; nerve regeneration; neural regeneration; neuroprotection; progesterone; traumatic brain injury; western blotting