Infection-induced vulnerability of perinatal brain injury

Abstract

A growing body of evidence demonstrates that susceptibility and progression of both acute and chronic central nervous system disease in the newborn is closely associated with an innate immune response that can manifest from either direct infection and/or infection-triggered damage. A common feature of many of these diseases is the systemic exposure of the neonate to bacterial infections that elicit brain inflammation. In recent years, the importance of innate immune receptors in newborn brain injury, the so-called Toll-like receptors, has been demonstrated. In this paper we will discuss how neonatal sepsis, with particular emphasis on Escherichia coli, coagulase-negative staphylococci, and group B streptococcal infections in preterm infants, and Toll-like receptor-mediated inflammation can increase the vulnerability of the newborn brain to injury.

Figure 1

Diagram outlining infectious agents, TLRs, and major signaling pathways. Abbreviations: SE: S. epidermidis; GBS: group B streptococcus; LPT: lipopeptides. LPS: lipopolysaccharide; MyD88: myeloid differentiation primary response gene (88); TRIF: TIR domain-containing adaptor inducing interferon-β-mediated transcription factor; NF-κB: nuclear factor-KappaB; IRF: interferon regulatory factor; IP-10: interferon gamma-induced protein 10; IFN: interferon; TNF: tumor necrosis factor; IL-1: Interleukin -1.