Sex Differences in Gene and Protein Expression After Intracerebral Hemorrhage in Mice
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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.
KeywordsMouse 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.
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
- 11.James ML, Warner DS, Laskowitz DT Preclinical models of intracerebral hemorrhage: a translational perspective. Neurocrit Care. 2007.Google Scholar
- 12.Lei B, Sheng H, Wang H, Lascola CD, Warner DS, Laskowitz DT, James ML Intrastriatal injection of autologous blood or clostridial collagenase as murine models of intracerebral hemorrhage. J Vis Exp. 2014 (89). doi: https://doi.org/10.3791/51439.
- 13.Rosenberg GA, Estrada E, Wesley M, Kyner WT. Autoradiographic patterns of brain interstitial fluid flow after collagenase-induced haemorrhage in rat. Acta Neurochir Suppl (Wien). 1990;51:280–2.Google Scholar
- 14.Caligioni CS Assessing reproductive status/stages in mice. Curr Protoc Neurosci. 2009.Google Scholar
- 19.Toyo-oka K, Wachi T, Hunt RF, Baraban SC, Taya S, Ramshaw H, et al. 14-3-3epsilon and zeta regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain. J Neurosci Off J Soc Neurosci. 2014;34(36):12168–81. https://doi.org/10.1523/JNEUROSCI.2513-13.2014.CrossRefGoogle Scholar
- 20.Shen EY, Ahern TH, Cheung I, Straubhaar J, Dincer A, Houston I, et al. Epigenetics and sex differences in the brain: a genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice. Exp Neurol. 2015;268:21–9. https://doi.org/10.1016/j.expneurol.2014.08.006.CrossRefGoogle Scholar
- 22.White RE, Palm C, Xu L, Ling E, Ginsburg M, Daigle BJ et al. Mice lacking the beta2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia. ASN Neuro. 2012. 4(5). doi: https://doi.org/10.1042/AN20110020