Cerebral gray matter injuries in infants with intraventricular hemorrhage

Abstract

While intraventricular hemorrhage (IVH) predominantly damages the periventricular white matter, it induces substantial injury to the cerebral gray matter. IVH destroys the germinal matrix, suppresses neurogenesis, and disrupts corticogenesis, thereby reducing the number of neurons in the upper cortical layer and volume of the cerebral gray matter. The pathogenesis of gray matter injury is attributed to IVH-induced oxidative stress, inflammation, and mass effect damaging the germinal matrix as well as to post-hemorrhagic ventricular dilation (PHVD). The IVH-induced cerebral gray matter injury and PHVD contribute to cognitive deficits and neurobehavioral disorders. Neuroimaging has enhanced our understanding of cerebral gray matter injury and is a valuable predictor of neurodevelopmental outcomes. Evidence from therapies tested in preclinical models and clinical trials suggests that strategies to promote neurogenesis, reduce cerebral inflammation and oxidative stress, and remove blood clots from the ventricles might enhance the outcome of these infants. This review offers an integrated view of new insights into the mechanisms underlying gray matter injury in premature infants with IVH and highlights the imminent therapies to restore neurodevelopmental dysfunction in IVH survivors.