The effect of progesterone dose on gene expression after traumatic brain injury

Gail D. Anderson, Federico M. Farin, Theo K. Bammler, Richard P. Beyer, Alicia A. Swan, Hui Wen Wilkerson, Eric D. Kantor, Michael R. Hoane

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10mg/kg or 20mg/kg given i.p.) was started 4h post-injury and administered every 12h post-injury for up to 72h, with the last injection 12hr prior to death for the 24h and 72h groups. In the CCI-injured vehicle group compared to non-injured animals, expression of 1,114, 4,229, and 291 distinct genes changed >1.5-fold (p<0.05) at 24h, 72h, and 7 days, respectively. At 24h, the effect of low-dose progesterone on differentially expressed genes was <20% the effect of higher dose compared to vehicle. GO analysis identified a significant effect of low- and high-dose progesterone treatment compared to vehicle on DNA damage response. At 72h, high-dose progesterone treatment compared to vehicle affected expression of almost twice as many genes as did low-dose progesterone. Both low- and high-dose progesterone resulted in expression of genes regulating inflammatory response and apoptosis. At 7 days, there was only a modest difference in high-dose progesterone compared to vehicle, with only 14 differentially expressed genes. In contrast, low-dose progesterone resulted in 551 differentially expressed genes compared to vehicle. GO analysis identified genes for the low-dose treatment involved in positive regulation of cell proliferation, innate immune response, positive regulation of anti-apoptosis, and blood vessel remodeling.

Original languageEnglish (US)
Pages (from-to)1827-1843
Number of pages17
JournalJournal of Neurotrauma
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • CCI injury model
  • gene expression
  • neurotrauma
  • progesterone

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Anderson, G. D., Farin, F. M., Bammler, T. K., Beyer, R. P., Swan, A. A., Wilkerson, H. W., Kantor, E. D., & Hoane, M. R. (2011). The effect of progesterone dose on gene expression after traumatic brain injury. Journal of Neurotrauma, 28(9), 1827-1843. https://doi.org/10.1089/neu.2011.1911