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(Stroke. 2007;38:724.)
© 2007 American Heart Association, Inc.

Cerebral Ischemia and the Developing Brain: Introduction

Maturation-Dependent Vulnerability of Perinatal White Matter in Premature Birth

Stephen A. Back, MD, PhD; Art Riddle, BS Melissa M. McClure, PhD

From the Departments of Pediatrics and Neurology, Oregon Health & Science University, Portland, Ore.

Correspondence to Dr Stephen A. Back, Department of Pediatrics, Oregon Health & Science University, HRC-5, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3098. E-mail Backs{at}ohsu.edu

Abstract

Survivors of premature birth have a predilection for perinatal brain injury, especially to periventricular cerebral white matter. Periventricular white matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia) and diffuse myelination disturbances. Recent neuroimaging studies support that the incidence of periventricular leukomalacia is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical–mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary but not sufficient to generate the initial injury that leads to PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. There has been substantial recent progress in the understanding of the cellular and molecular pathogenesis of PWMI. The oligodendrocyte progenitor is a key target for preventive strategies to reduce ischemic cerebral white matter injury in premature infants.

Key Words: hypoxia-ischemia • oligodendrocyte • prematurity

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