Central nervous system (CNS) infections remain a major burden of pediatric disease associated with significant long-term morbidity due to injury to the developing brain. Children are susceptible to various etiologies of CNS infection partly because of vulnerabilities in their peripheral immune system. Young children are known to have reduced numbers and functionality of innate and adaptive immune cells, poorer production of immune mediators, impaired responses to inflammatory stimuli and depressed antibody activity in comparison to adults. This has implications not only for their response to pathogen invasion, but also for the development of appropriate vaccines and vaccination strategies. Further, pediatric immune characteristics evolve across the span of childhood into adolescence as their broader physiological and hormonal landscape develop. In addition to intrinsic vulnerabilities, children are subject to external factors that impact their susceptibility to infections, including maternal immunity and exposure, and nutrition. In this review we summarize the current evidence for immune characteristics across childhood that render children at risk for CNS infection and introduce the link with the CNS through the modulatory role that the brain has on the immune response. This manuscript lays the foundation from which we explore the specifics of infection and inflammation within the CNS and the consequences to the maturing brain in part two of this review series.
The pauci-cellular nature of cerebrospinal (CSF), particularly ventricular CSF, and the rapid cell death following sampling, incumbers the use of flow cytometric analysis of these samples in the investigation of central nervous system (CNS) pathologies. Developing a method that allows long-term storage and batched analysis of CSF samples without compromising cell integrity is highly desirable in clinical research, given that CSF is often sampled after hours creating logistical difficulties for fresh processing. We examined percentages and relative proportion of peripheral and brain-derived immune cells in Cryopreserved and Transfix-treated CSF, compared to freshly processed CSF. Cell proportions were more comparable between Fresh and Cryopreserved CSF (mean of differences = 3.19), than between Fresh and Transfix-treated CSF (mean of differences = 14.82). No significant differences in cell percentages were observed in Fresh versus Cryopreserved CSF; however significantly lower cell percentages were observed in Transfix-treated CSF compared to Fresh CSF [(CD11b++ (p = 0.01), CD4+ (p = 0.001), CD8+ (p = 0.007), NK cells (p = 0.04), as well as CD69+ activation marker (p = 0.001)]. Furthermore, loss of marker expression of various lymphocyte sub-populations were observed in Transfix-treated CSF. Cryopreservation is a feasible option for long-term storage of ventricular CSF and allows accurate immunophenotyping of peripheral and brain-derived cell populations by flow cytometry.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.