A Review of Pre-Clinical Studies for the Treatment of Neonatal Brain Injury

Bryan Kolb,Preston Williams

doi:10.31487/j.nnb.2020.01.07

Abstract

The developing brain is especially sensitive to perturbations such as hypoxia-ischemia (HI) or surgical ablation in the perinatal period. We first review and contrast the effects perinatal HI and surgical perturbation in laboratory rats. The developing brain is also very responsive to a wide range of other experiences that can induce remarkable neural plasticity in both the normal and perinatally injured brain. We next review the factors that influence this plasticity in both the normal and perinatal injured. We consider treatments that stimulate cerebral and behavioural plasticity, especially in the motor systems. The goal is to draw attention to possible treatments that could be translated from perinatal surgical ablation to the HI model and eventually to the clinic.

Highlights

The incidence of brain injury in babies is relatively high ranging from about 3 per 1000 in full term infants to about 25 per 1000 in preterm births [1, 2]
We briefly review the stages of brain development and neural plasticity before examining models of perinatal brain injury and the major factors that modulate brain development after perinatal surgical ablation and HI brain injury
Because the HI model studies have often been focussed more on cerebral palsy, which is associated with significant motor disturbances, our emphasis is on examination of motor system plasticity in both the surgical ablation and HI studies

Summary

Introduction

The incidence of brain injury in babies is relatively high ranging from about 3 per 1000 in full term infants to about 25 per 1000 in preterm births (babies born at or less than 37 weeks) [1, 2]. Kennard did not study the postinjury changes in the brain of her monkeys, she did speculate on possible effects of the injuries on synaptic organization It was Kennard’s studies that led to the idea that postnatal cortical injury early in development is associated with a better outcome than surgery later, an idea often referred to as the “Kennard Principle.”. Bland & Cooper first showed that housing rats in complex environments after perinatal ablation of the visual cortex significantly improved functional outcome and this finding was later replicated in kittens with occipital ablations [69, 70] This general effect has been replicated numerous times in animals with perinatal injuries in other cortical regions such as motor or medial prefrontal cortex.

Gestational FGF-2

Conclusions