Neuroprotection Strategies in Preterm Encephalopathy

Abstract

Advances in neonatology have led to unprecedented improvements in neonatal survival such that those born as early as 22 weeks of gestation now have some chance of survival, and over 70% of those born at 24 weeks of gestation survive. Up to 50% of infants born extremely preterm develop poor outcomes involving long-term neurodevelopmental impairments affecting cognition and learning, or motor problems such as cerebral palsy. Poor outcomes arise because the preterm brain is vulnerable both to direct injury (by events such as intracerebral hemorrhage, infection, and/or hypoxia), or indirect injury due to disruption of normal development. This neonatal brain injury and/or dysmaturation is called "encephalopathy of prematurity". Current and future strategies to improve outcomes in this population include prevention of preterm birth, and pre-, peri-, and postnatal approaches to protect the developing brain. This review will describe mechanisms of preterm brain injury, and current and upcoming therapies in the antepartum and postnatal period to improve preterm encephalopathy.

Figure 1.. Schematic of human brain development.

(A) Sequence of brain maturation from conception to adulthood. (B) Human neuronal cell development during the life time. (C) Cortical Development in the third trimester of preterm and term infants. MZ: marginal zone, CP: cortical plate, SP: sub plate layer, IZ: intermediate zone, WM: white matter, SVZ: subventricular zone, VZ: ventricular zone.

Figure 2.. Flow diagram outlining risk factor and underlying mechanism contributing to preterm encephalopathy.

Mentioned risk factors lead to hypoxia-ischemia, inflammation and oxidative stress, which causes white and gray matter injury by different mechanisms and ultimately lead to long term cognitive and motor impairment.