Diversity Supplement: Anti-oxidant Promoting Cytokine LIF Enhances Neural Cell Survival During Ischemia

The splenic inflammatory response elicited partially through IFNƒ×ƒncontributes to the expansion of the ischemic injury in rodent models of stroke. Leukemia inhibitory factor (LIF), a cytokine that alters the phenotype of T cells and macrophages towards an anti-inflammatory state, inhibits splenic-derived IFNƒ× in young male Sprague- Dawley rats after stroke, thus decreasing neural injury. However, basal splenic IFNƒ×ƒnexpression isƒn7-8-fold higher in aged rats, and stroke-induced IFNƒ×ƒnis inhibited by LIF in aged females but not in aged males. In addition, LIF treatment produces partial functional recovery, but only in aged females. Our preliminary data also show that IFNƒ×ƒyƒnsplenic T cells are autoreactive to CNS antigens in young male mice, but we do not know if this peripheral CNS-directed post-stroke autoimmune response occurs with aging. We surmise that the immune system¡¦s response to stroke, originating from the spleen, differs with age and between aged male and female rodents. We hypothesize that targetingƒn IFNƒ× producing T cells will be protective in aged females but not aged males after experimental stroke. This hypothesis supports the following Aims. Specific Aim 1: To determine sex differences in immune cell phenotypes in aged rats. This Aim will determine the types of immune cells that are responding to stroke in aged male and female rats and identify the cells that mediate therapeutic efficacy of LIF in the female tissues. This study has implications beyond stroke pathology in that understanding sex differences directly affects treatment for any pathology related to the peripheral immune response.