Estrone is neuroprotective in rats after traumatic brain injury

Joshua W. Gatson, Ming Mei Liu, Kareem Abdelfattah, Jane G. Wigginton, Scott Smith, Steven Wolf, James W. Simpkins, Joseph P. Minei

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (p<0.01) and neuronal injury (p<0.001), and it reduced cerebral cortical levels of TUNEL-positive staining (p<0.0001), and decreased numbers of TUNEL-positive cells in the corpus callosum (p<0.03). We assessed the levels of β-amyloid in the injured animals and found that estrone significantly decreased the cortical levels of β-amyloid after brain injury. Cortical levels of phospho-ERK1/2 were significantly (p<0.01) increased by estrone. This increase was associated with an increase in phospho-CREB levels (p<0.021), and brain-derived neurotrophic factor (BDNF) expression (p<0.0006). In conclusion, estrone given acutely after injury increases the signaling of protective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

Original languageEnglish (US)
Pages (from-to)2209-2219
Number of pages11
JournalJournal of Neurotrauma
Volume29
Issue number12
DOIs
StatePublished - Aug 10 2012
Externally publishedYes

Keywords

  • brain-derived neurotrophic factor
  • estrone
  • extracellular signal-regulated kinase (erk)
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Gatson, J. W., Liu, M. M., Abdelfattah, K., Wigginton, J. G., Smith, S., Wolf, S., Simpkins, J. W., & Minei, J. P. (2012). Estrone is neuroprotective in rats after traumatic brain injury. Journal of Neurotrauma, 29(12), 2209-2219. https://doi.org/10.1089/neu.2011.2274