Delineating The Role Of Sex Chromosome And Hormones In Intraspinal Inflammation and Pain After SCI

Abstract: Sex chromosomes, in addition to hormones, are a primary determinant of biological sex but have been largely overlooked by the spinal cord injury field. Genes residing on sex chromosomes likely contribute to the sex bias in autoimmune disorders and sex-specific inflammatory responses [6]. Through chromosomal mapping, Dominguez et al provided strong support for a significant genetic component to the differential development of pain between male and female rats after SCI [7]. To the best of our knowledge, Dominguez et al. is the only report of this nature in SCI implicating sex chromosomes in sexual dimorphisms after SCI. The unexplored role of sex chromosomes in SCI pathology along with numerous observations of differences between males and females regarding intraspinal inflammation and pain [1-4, 8- 11] form the rationale and foundation for this pilot proposal. Specifically, in Aim 1, we propose using the Four Core Genotypes (FCG) mouse model [12-14], which generates XX and XY female mice with ovaries, and XX and XY male mice with testes, to define the role of sex chromosomes on SCI sexual dimorphisms. Further, in Aim 2, we will investigate sex-specific inflammatory responses in pig and mouse SCI models using a novel immunohistochemical (IHC) approach ideally suited for large animal studies.