Targeting Microglial Disturbances to Protect the Brain From Neurodevelopmental Disorders Associated With Prematurity

Abstract

Microglial activation during critical phases of brain development can result in short- and long-term consequences for neurological and psychiatric health. Several studies in humans and rodents have shown that microglial activation, leading to a transition from the homeostatic state toward a proinflammatory phenotype, has adverse effects on the developing brain and neurodevelopmental disorders. Targeting proinflammatory microglia may be an effective strategy for protecting the brain and attenuating neurodevelopmental disorders induced by inflammation. In this review we focus on the role of inflammation and the activation of immature microglia (pre-microglia) soon after birth in prematurity-associated neurodevelopmental disorders, and the specific features of pre-microglia during development. We also highlight the relevance of immunomodulatory strategies for regulating activated microglia in a rodent model of perinatal brain injury. An original neuroprotective approach involving a nanoparticle-based therapy and targeting microglia, with the aim of improving myelination and protecting the developing brain, is also addressed.