Principles of Perinatal Hypoxic-Ischemic Brain Injury

Abstract

Abstract The pathogenesis of injury to the developing brain encompasses low oxygen tension and decreased perfusion, often termed hypoxia-ischemia. Factors playing key roles in this setting include (1) inherent vulnerability of immature cells to conditions such as oxidative stress, cytokines, and excitotoxicity; (2) imperfect autoregulation of cerebral blood flow in the face of fluctuations in systemic perfusion pressure, especially in prematurity; (3) presence of blood products in direct contact with developing brain regions, such as the germinal matrix and cerebellum; (4) frequent co-occurrence of other serious illnesses, such as lung disease in the premature infant, or congenital heart disease in the term infant; and (5) significant antenatal conditions, for example, maternal pre-eclampsia with chronic placental hypoperfusion, or acute chorioamnionitis precipitating preterm delivery. The totality of neuropathology experienced by an infant is a summation over time of all of the above circumstances, which may be singular, intermittent, or continuous, or, most likely, a combination thereof. This article will attempt to shed light on the spectrum of injury seen in the perinatal brain and will comprise lesions encountered in the stillborn, the premature, and the term infant through the presentation of 4 illustrative case studies. These include a term stillbirth with diffuse white matter gliosis and selective neuronal vulnerability (pontosubicular necrosis); a 3-week-old premature infant with periventricular leukomalacia and thalamic/basal ganglionic injury; a premature infant with germinal matrix hemorrhage, complicated by periventricular hemorrhagic infarction; and a term infant with congenital heart disease requiring extracorporeal membrane oxygenation therapy, and global hypoxic-ischemic encephalopathy.