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

32 Citations (Scopus)

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

Fingerprint

Progesterone
Gene Expression
Gene Ontology
Genes
Traumatic Brain Injury
Wounds and Injuries
Therapeutics
Innate Immunity
DNA Damage
Blood Vessels
Cell Proliferation
Apoptosis
Injections

Keywords

  • CCI injury model
  • gene expression
  • neurotrauma
  • progesterone

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Anderson, G. D., Farin, F. M., Bammler, T. K., Beyer, R. P., Swan, A. A., Wilkerson, H. W., ... 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

The effect of progesterone dose on gene expression after traumatic brain injury. / Anderson, Gail D.; Farin, Federico M.; Bammler, Theo K.; Beyer, Richard P.; Swan, Alicia A.; Wilkerson, Hui Wen; Kantor, Eric D.; Hoane, Michael R.

In: Journal of Neurotrauma, Vol. 28, No. 9, 01.09.2011, p. 1827-1843.

Research output: Contribution to journalArticle

Anderson, GD, Farin, FM, Bammler, TK, Beyer, RP, Swan, AA, Wilkerson, HW, Kantor, ED & Hoane, MR 2011, 'The effect of progesterone dose on gene expression after traumatic brain injury', Journal of Neurotrauma, vol. 28, no. 9, pp. 1827-1843. https://doi.org/10.1089/neu.2011.1911
Anderson GD, Farin FM, Bammler TK, Beyer RP, Swan AA, Wilkerson HW et al. The effect of progesterone dose on gene expression after traumatic brain injury. Journal of Neurotrauma. 2011 Sep 1;28(9):1827-1843. https://doi.org/10.1089/neu.2011.1911
Anderson, Gail D. ; Farin, Federico M. ; Bammler, Theo K. ; Beyer, Richard P. ; Swan, Alicia A. ; Wilkerson, Hui Wen ; Kantor, Eric D. ; Hoane, Michael R. / The effect of progesterone dose on gene expression after traumatic brain injury. In: Journal of Neurotrauma. 2011 ; Vol. 28, No. 9. pp. 1827-1843.
@article{835a8c98888245d8934a9ffecf337e59,
title = "The effect of progesterone dose on gene expression after traumatic brain injury",
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.",
keywords = "CCI injury model, gene expression, neurotrauma, progesterone",
author = "Anderson, {Gail D.} and Farin, {Federico M.} and Bammler, {Theo K.} and Beyer, {Richard P.} and Swan, {Alicia A.} and Wilkerson, {Hui Wen} and Kantor, {Eric D.} and Hoane, {Michael R.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1089/neu.2011.1911",
language = "English (US)",
volume = "28",
pages = "1827--1843",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "9",

}

TY - JOUR

T1 - The effect of progesterone dose on gene expression after traumatic brain injury

AU - Anderson, Gail D.

AU - Farin, Federico M.

AU - Bammler, Theo K.

AU - Beyer, Richard P.

AU - Swan, Alicia A.

AU - Wilkerson, Hui Wen

AU - Kantor, Eric D.

AU - Hoane, Michael R.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

KW - CCI injury model

KW - gene expression

KW - neurotrauma

KW - progesterone

UR - http://www.scopus.com/inward/record.url?scp=80054794856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054794856&partnerID=8YFLogxK

U2 - 10.1089/neu.2011.1911

DO - 10.1089/neu.2011.1911

M3 - Article

C2 - 21770760

AN - SCOPUS:80054794856

VL - 28

SP - 1827

EP - 1843

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 9

ER -