The challenge of understanding cerebral white matter injury in the premature infant

Abstract

White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30 years, there remain no proven therapies for the premature infant beyond supportive care. The lack of translational progress may be partially explained by the challenge of developing relevant animal models when the etiology remains unclear, as is the case in this disorder. There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant.

Why do premature newborn infants display elevated blood adenosine levels?

“…In fact, an over functioning OXPHOS is a primary source of ROS [32]. Premyelinating axons are particula r ly sensitive to oxidative stress, recently implicated in OPC death [4]. The oligodendrocyte lineage in the human premature brain is a vulnerable cell population (reviewed in [33]).…”

“…Since the 1960s (Banker and Larroche, 1962) unique VLBW infant white matter lesions have been described, consisting of coagulative necrosis known as periventricular leukomalacia (PVL). Recently, association of PVL with inflammation (O'Shea et al, 2013) and oxidative stress [4] was reported. Studies on titration of supplemental oxygen are suggestive of a primary role of hyperoxia in these lesions [5].…”

Gut microbiota, the immune system, and diet influence the neonatal gut–brain axis

“…Central nervous system injury in preterm infants often localizes to the white matter tracts (i.e., connectome) in the brain (105). Hence, imaging techniques that define injury to the connectome is receiving high interest (106,107).…”

Brain Injury in Preterm Infants: Pathogenesis and Nursing Implications

“…Focal lesion involve degeneration of axons and glia in the injured area. 4,21 Microscopic injuries are more common than cystic injuries (which tend to be more severe). 1,4 Diffuse PVL is characterized by damage to pre-myelinating oligodendrocytes (pre-OL) leading to hypomyelination, astrocystosis and microgliosis.…”