Translational Stroke Research

, Volume 10, Issue 2, pp 231–239 | Cite as

Sex Differences in Gene and Protein Expression After Intracerebral Hemorrhage in Mice

  • Yongqiu Xie
  • Yi-Ju Li
  • Beilei Lei
  • Dawn Kernagis
  • Wen-Wei Liu
  • Ellen R. Bennett
  • Talagnair Venkatraman
  • Christopher D. Lascola
  • Daniel T. Laskowitz
  • David S. Warner
  • Michael L. JamesEmail author
Original Article


Sex dimorphism has been demonstrated after experimental intracerebral hemorrhage (ICH). Decreased mortality and improved neurobehavioral outcomes occur in female compared to male mice after intrastriatal autologous blood or collagenase injection. Sex-specific differences in post-ICH gene and protein expression may provide mechanistic insight into this phenomenon. Ten- to 12-week-old C57BL/6 male (M) and female in high estrous state (HE-F) underwent left intrastriatal collagenase injection. We assessed neurobehavioral outcomes over the first 30 days, hematoma volume and cerebral edema evolution over the first 24 h, and transcriptomic gene and protein expression at pre-selected time points during the acute phase of injury. Genome-wide expression profiling was performed with Affymetrix GeneChip Mouse Genome 2.0 Probes, and proteomics analyses were performed using mass spectroscopy. Sex does not affect hemorrhage evolution, but female sex is associated with improved neurobehavioral recovery after ICH. A total of 7037 probes qualified for our filtering criteria, representing 5382 mapped genes and 256 unmapped genes. Female-unique pathways involved cell development, growth, and proliferation, while male-unique pathways involved molecular degradation. At 6 and 24 h post-ICH, differential expression was observed in 850 proteins vs baseline in males, 608 proteins vs baseline in females, and 1 protein in females vs males. Female sex is associated with improved neurobehavioral recovery, and differential gene and protein expression after intrastriatal collagenase injection.


Mouse model Intracerebral hemorrhage Proteomics Gene expression Sex differences 



We acknowledge Kathy Gage’s assistance in medical editing.


This work was funded by the Duke University Department of Anesthesiology Dream Innovation Grant (MLJ).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed.

Supplementary material

12975_2018_633_MOESM1_ESM.docx (490 kb)
Supplemental Figure 1 Differential gene expression in the acute phase response signaling pathway in female (A) and male (B) mice at 6 h after intracerebral hemorrhage compared to pre-injury baseline. Note: green = down-regulated SDE genes; red = up-regulated SDE genes; 6 h, 6 h after intracerebral hemorrhage; B, baseline; F, female; M, male. (DOCX 490 kb)
12975_2018_633_MOESM2_ESM.xlsx (74 kb)
Supplemental Table 1 Differentially expressed genes in female mice at selected time points after ICH compared to baseline. (XLSX 73 kb)
12975_2018_633_MOESM3_ESM.xlsx (429 kb)
Supplemental Table 2 Differentially expressed genes in male mice at selected time points after ICH compared to baseline. (XLSX 429 kb)
12975_2018_633_MOESM4_ESM.xlsx (17 kb)
Supplemental Table 3 Differentially expressed genes in male vs female mice at selected time points after ICH. (XLSX 17 kb)
12975_2018_633_MOESM5_ESM.xlsx (12 kb)
Supplemental Table 4 Top 10 pathways at each time point after ICH for male and female mice compared to baseline. (XLSX 12 kb)
12975_2018_633_MOESM6_ESM.xls (30 kb)
Supplemental Table 5 Differentially expressed genes enrolled in acute phase response signaling pathway in male vs female mice at selected time points after ICH. (XLS 30 kb)
12975_2018_633_MOESM7_ESM.xls (210 kb)
Supplemental Table 6 Differentially expressed proteins in male mice at selected time points after ICH compared to baseline. (XLS 210 kb)
12975_2018_633_MOESM8_ESM.xls (156 kb)
Supplemental Table 7 Differentially expressed proteins in female mice at selected time points after ICH compared to baseline. (XLS 156 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yongqiu Xie
    • 1
    • 2
  • Yi-Ju Li
    • 3
    • 4
    • 5
  • Beilei Lei
    • 2
    • 5
  • Dawn Kernagis
    • 5
    • 6
  • Wen-Wei Liu
    • 3
  • Ellen R. Bennett
    • 6
  • Talagnair Venkatraman
    • 2
    • 7
  • Christopher D. Lascola
    • 2
    • 7
  • Daniel T. Laskowitz
    • 2
    • 5
    • 6
    • 8
  • David S. Warner
    • 2
    • 5
    • 8
  • Michael L. James
    • 2
    • 5
    • 6
    Email author
  1. 1.Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Multidisciplinary Neuroprotection LaboratoriesDuke UniversityDurhamUSA
  3. 3.Department of Biostatistics and BioinformaticsDuke UniversityDurhamUSA
  4. 4.Duke Molecular Physiology InstituteDuke UniversityDurhamUSA
  5. 5.Department of AnesthesiologyDuke UniversityDurhamUSA
  6. 6.Department of NeurologyDuke UniversityDurhamUSA
  7. 7.Department of RadiologyDuke UniversityDurhamUSA
  8. 8.Department of NeurobiologyDuke UniversityDurhamUSA

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