Attenuated Inflammatory Response in Aged Mice Brains following Stroke

Background: Increased age is a major risk factor for stroke incidence, post-ischemic mortality, and severe and long-term disability. Stroke outcome is considerably influenced by post-ischemic mechanisms. We hypothesized that the inflammatory response following an ischemic injury is altered in aged organisms. Methods and Results: To that end, we analyzed the expression pattern of pro-inflammatory cytokines (TNF, IL-1a, IL-1b, IL-6), anti-inflammatory cytokines (IL-10, TGFb1), and chemokines (Mip-1a, MCP-1, RANTES) of adult (2 months) and aged (24 months) mice brains at different reperfusion times (6 h, 12 h, 24 h, 2 d, 7 d) following transient occlusion of the middle cerebral artery. The infarct size was assessed to monitor possible consequences of an altered inflammatory response in aged mice. Our data revealed an increased neuro-inflammation with age. Above all, we found profound age-related alterations in the reaction to stroke. The response of pro-inflammatory cytokines (TNF, and IL-1b) and the level of chemokines (Mip-1a, and MCP-1) were strongly diminished in the aged post-ischemic brain tissue. IL-6 showed the strongest age-dependent decrease in its post-ischemic expression profile. Anti-inflammatory cytokines (TGFb1, and IL-10) revealed no significant age dependency after ischemia. Aged mice brains tend to develop smaller infarcts. Conclusion: The attenuated inflammatory response to stroke in aged animals may contribute to their smaller infarcts. The results presented here highlight the importance of using aged animals to investigate age-associated diseases like stroke

Age at Menarche, Schooling, and Sexual Debut in Northern Malawi

Background: Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.Methods and Findings: A cross-sectional sexual behaviour survey was conducted on all individuals age 15-59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25(th) centile was used to define "early" sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (= 16 (OR 0.04, 95%CI 0.02-0.05) compared to those with menarche at = 16. The association between age at menarche and schooling was partly explained by age at sexual debut. The association between age at menarche and early sex was not altered by adjusting for schooling.Conclusions: Women with early menarche start sex and marry early, leading to school drop-out. It is important to find ways to support those who reach menarche early to access the same opportunities as other young women

Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed