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Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

引用

Neural Regeneration Research 2014年第21期9卷 1891-1896页

作者： Richard Justin Garling Lora Talley Watts Shane Sprague Lauren Fletcher David F.Jimenez Murat Digicaylioglu Department of Neurosurgery University of Texas Health Science CenterSan AntonioTXUSA Research Imaging Institute University of Texas Health Science CenterSan AntonioTXUSA Department of Cellular and Structural Biology University of Texas Health Science CenterSan AntonioTXUSA Department of Neurology University of Texas Health Science CenterSan AntonioTXUSA

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 neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia 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 harvest-ed at 72 hours post injury and prepared for western blot analysis. traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

关键词： nerve regeneration Akt traumatic brain injury progesterone apoptosis neuroprotec-tion brain injury western blotting controlled cortical impact neural regeneration

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