Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?

Abstract

This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy-like outcomes, and argues that much of this brain damage is preventable. We review the experimental evidence that there are treatments that can be safely administered to women in late pregnancy that decrease the likelihood and extent of perinatal brain damage that occurs because of acute and severe hypoxia that arises during some births, and the additional impact of chronic fetal hypoxia, infection, inflammation, growth restriction and preterm birth. We discuss the types of interventions required to ameliorate or even prevent apoptotic and necrotic cell death, and the vulnerability of all the major cell types in the brain (neurons, astrocytes, oligodendrocytes, microglia, cerebral vasculature) to hypoxia/ischaemia, and whether a pan-protective treatment given to the mother before birth is a realistic prospect.

Keywords: Oxidative stress; cerebral palsy; neuroprotection; perinatal brain damage; prophylaxis.

Figure 1. Oligodendrocyte progenitor cells (OPCs) undergo distinct changes as they mature into mature, myelinating oligodendrocytes

Different signals in the injured perinatal nervous system (e.g. hyaluronan, changes in neurosteroids) influence maturation at different stages.