Fetal inflammatory response and brain injury in the preterm newborn

Abstract

Preterm birth can be caused by intrauterine infection and maternal/fetal inflammatory responses. Maternal inflammation (chorioamnionitis) is often followed by a systemic fetal inflammatory response characterized by elevated levels of proinflammatory cytokines in the fetal circulation. The inflammation signal is likely transmitted across the blood-brain barrier and initiates a neuroinflammatory response. Microglial activation has a central role in this process and triggers excitotoxic, inflammatory, and oxidative damage in the developing brain. Neuroinflammation can persist over a period of time and sensitize the brain to subinjurious insults in early and chronic phases but may offer relative tolerance in the intermediate period through activation of endogenous anti-inflammatory, protective, and repair mechanisms. Neuroinflammatory injury not only destroys what exists but also changes what develops.

Figure 1

The traditional scenario of perinatal brain injury (A) postulates that a single and rather short insult damages existing structure and leads to altered function. We propose the alternative view (B), which postulates that after an initial trigger has occurred, an ongoing interaction between innate and adaptive immune processes adversely affects the development of brain structure and function over an extended period of time.