Cerebral Inflammation and Sex Differences in Young Rodents Exposed to a Low Resourced Environment May Predict the Onset of Hypertension in Adulthood

Introduction: Adverse Childhood Experiences (ACEs) are associated with negative health outcomes as children progress to adults. Poverty, a type of ACE, impacts 16 million children annually in the USA. Childhood poverty is associated with hypertension (HTN) and increased inflammation in adulthood. To mimic poverty, we utilized the Limited Bedding and Nesting (LBN) rodent model during weaning. Previous studies from our lab show that adult male (M) rats exposed to a low resourced environment have elevated blood pressure and cerebral inflammation, while females (F) display no changes. This suggests that inflammation may contribute to HTN in LBN M. The onset of these inflammatory changes is unknown. We hypothesize that M, and not F, rats exposed to LBN treatment, will exhibit an increase in pro-inflammatory cytokines and decrease in anti-inflammatory cytokines in childhood. Methods: Pregnant Sprague Dawley dams and their pups were either exposed to a normal environment of bedding and nesting or LBN on postnatal days 2-9. After weaning, rats were grouped by sex and experimental status: LBN M, LBN F, CON M, and CON F (n=6-7/group). At 4 weeks (childhood), brains were collected and used to assay pro-inflammatory cytokines [interleukin 17 (IL-17), tumor necrosis factor alpha (TNFα), and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10). Results: IL-17 was increased in LBN M vs CON M (814 ± 141 vs 421 ± 39, p=0.04) and trending downward in LBN F vs CON F (352 ± 41 vs 692 ± 149, ns). TNFα was elevated in F vs M in both LBN and CON rats (F (1,19) = 44; p<0.0001). Moreover, there was no difference in TNFα in LBN vs CON in M or F. No changes were observed in IL-6 between M and F, however, there was a 5-fold decrease in IL-6 in LBN F vs CON F (567 ± 153 vs 3066 ± 593, p=0.002). Both anti-inflammatory cytokines, IL-10 (F (1,14) = 5.2; p=0.038) and IL-4 (F (1,20) = 8.8; p=0.007) [MC1] were increased in F vs M in both LBN and CON rats. Discussion: In summary, LBN M may have an increase in cerebral inflammation, due to an increase in IL-17 compared to CON M. LBN F may have a decrease in inflammation due to a decrease in IL-17 and IL-6, and an increase in IL-4 and IL-10 compared to CON F. Surprisingly, F had elevated TNFα concentrations compared to M. Despite increases in TNFα, F appeared to be protected against an increase in cerebral inflammation, due to an overall anti-inflammatory state. These sex differences in cerebral inflammation, linked to rodent models of early life stress, may provide insights into novel biomarkers and predictive factors that contribute to HTN development. Childhood poverty has long lasting effects on one’s health that could persist throughout one’s lifetime. Thus, early interventions are crucial to ensuring that every child has a chance for a healthier future. This research was supported by start-up funds and the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)]. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.