Elevated Cerebral Anti-Inflammation and Antioxidant Capacity in Prepubescent Female Rodents Exposed to a Poverty-Like Stressor May Provide Protection Against Hypertension in Adulthood

Adverse Childhood Experiences, which affect over 60% of the US population, are Early Life Stress (ELS) events that include abuse, neglect, violence, household dysfunction, and poverty. Poverty, a state of resource deprivation, is a major public health concern that impacts 1 in 6 US children. Adults who experienced childhood poverty have an increased risk for hypertension (HTN) with sex differences. The sex-dependent onset of HTN may be due to alterations in cerebral inflammation and oxidative stress. Recently published data by our group show that male rodents exposed to the Limited Bedding and Nesting (LBN) model, which induces resource deprivation ELS, developed HTN in adulthood, while females did not. The drivers of these sex differences are unknown, so we aimed to examine cerebral inflammation and oxidative stress in rodents before puberty and the onset of HTN. We hypothesize that prepubescent female rats will be protected from an increase in cerebral inflammation and oxidative stress when exposed to a resource deprivation ELS. METHODS: Rodent dams and pups were exposed to normal bedding (CON) or LBN on postnatal days 2-9. After weaning, rats were grouped: LBN Females (F), CON F, LBN Males (M), or CON M (n=6-7/group). At 4 weeks of age, (equivalent to early childhood in humans) pup brains were collected and used to assay pro-inflammatory [interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10). Oxidative stress was evaluated by measuring cerebral hydrogen peroxide (H 2 O 2 ) levels and total antioxidant capacity (TAC). RESULTS: There were no alterations in pro-inflammatory IL-6 and IL-17 comparing F and M, but there was an elevation in TNF-α in F (p=.0001). TNF-α and IL-17 were unchanged, but IL-6 was drastically reduced, five-fold, in LBN F vs CON F (567 ±153 vs 3070 ±593 pg/mg protein, p=.002). Conversely, in LBN M vs CON M, there were no changes in TNF-α and IL-6, but there was doubled IL-17 in LBN M (814 ±141 vs 421 ±39 pg/mg protein, p=.07). Both anti-inflammatory cytokines (IL-10 and IL-4) and TAC were increased in F vs M regardless of LBN exposure (p=.007; p=.04; p=.01). No changes in H 2 O 2 were observed. DISCUSSION: The increase in both anti-inflammatory cytokines and antioxidant capacity in young F rodents may prevent the onset of HTN as adults, despite LBN exposure. Furthermore, the decrease in IL-6 in LBN F and increase in IL-17 in LBN M suggest that F exhibit a cerebral anti-inflammatory state, while M display a cerebral pro-inflammatory state at a young age. In summary, alterations in cerebral inflammation and oxidative stress in young ELS F may protect them from the HTN observed in adult M that experience ELS. These findings are clinically relevant as they provide insights into the sex differences in brain inflammation and oxidative stress before puberty, which may contribute to the pathogenesis of HTN in adults exposed to ACEs, such as childhood poverty. This abstract was presented at the American Physiology Summit 2026 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.