This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Back, S. A. Articles by McClure, M. M. Search for Related Content PubMed PubMed Citation Articles by Back, S. A. Articles by McClure, M. M. Related Collections Animal models of human disease

(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

This article has been cited by other articles:

				C. O. Chua, H. Chahboune, A. Braun, K. Dummula, C. E. Chua, J. Yu, Z. Ungvari, A. A. Sherbany, F. Hyder, and P. Ballabh Consequences of Intraventricular Hemorrhage in a Rabbit Pup Model * Supplemental Methods Stroke, October 1, 2009; 40(10): 3369 - 3377. [Abstract] [Full Text] [PDF]

				A. Desfeux, F. El Ghazi, S. Jegou, H. Legros, S. Marret, V. Laudenbach, and B. J. Gonzalez Dual Effect of Glutamate on GABAergic Interneuron Survival during Cerebral Cortex Development in Mice Neonates Cereb Cortex, September 16, 2009; (2009) bhp181v1. [Abstract] [Full Text] [PDF]

				Xiaoyang Wang, G. Hellgren, C. Lofqvist, Wenli Li, A. Hellstrom, H. Hagberg, and C. Mallard White Matter Damage After Chronic Subclinical Inflammation in Newborn Mice J Child Neurol, September 1, 2009; 24(9): 1171 - 1178. [Abstract] [PDF]

				S. Malaeb and O. Dammann Fetal Inflammatory Response and Brain Injury in the Preterm Newborn J Child Neurol, September 1, 2009; 24(9): 1119 - 1126. [Abstract] [PDF]

				J. D. Yeatman, M. Ben-Shachar, R. Bammer, and H. M. Feldman Using Diffusion Tensor Imaging and Fiber Tracking to Characterize Diffuse Perinatal White Matter Injury: A Case Report J Child Neurol, July 1, 2009; 24(7): 795 - 800. [Abstract] [PDF]

				C. F. Hagmann, E. De Vita, A. Bainbridge, R. Gunny, A. B. Kapetanakis, W. K. Chong, E. B. Cady, D. G. Gadian, and N. J. Robertson T2 at MR Imaging Is an Objective Quantitative Measure of Cerebral White Matter Signal Intensity Abnormality in Preterm Infants at Term-equivalent Age Radiology, July 1, 2009; 252(1): 209 - 217. [Abstract] [Full Text] [PDF]

				W. Deng, J. Pleasure, and D. Pleasure Progress in Periventricular Leukomalacia Arch Neurol, October 1, 2008; 65(10): 1291 - 1295. [Abstract] [Full Text] [PDF]

				O Khwaja and J J Volpe Pathogenesis of cerebral white matter injury of prematurity Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2008; 93(2): F153 - F161. [Abstract] [Full Text] [PDF]

				G. Wassink, L. Bennet, L. C. Booth, E. C. Jensen, B. Wibbens, J. M. Dean, and A. J. Gunn The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep J Appl Physiol, October 1, 2007; 103(4): 1311 - 1317. [Abstract] [Full Text] [PDF]