Perinatal Hypoxia-Ischemia Induces Apoptotic and Excitotoxic Death of Periventricular White Matter Oligodendrocyte ProgenitorsNess J.K. · Romanko M.J. · Rothstein R.P. · Wood T.L. · Levison S.W.
Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia.
© 2001 S. Karger AG, Basel
- Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC: Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci 2001;21:1302–1312.
- Volpe J: Brain injury in the premature infant – From pathogenesis to prevention. Brain Dev 1997;19:519–534.
- Back S, Volpe J: Cellular and molecular pathogenesis of periventricular white matter injury. Ment Retard Dev Disabil Res Rev 1997;3:96–107.
- Perlman JM: White matter injury in the preterm infant: An important determination of abnormal neurodevelopmental outcome. Early Hum Dev 1998;53:99–120.
- Back S, Gan X, Li Y, Rosenberg P, Volpe J: Maturation-dependant vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci 1998;18:6241–6253.
- Yoshioka A, Hardy M, Younkin D, Grinspan J, Stern J, Pleasure D: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage. J Neurochem 1995;64:2442–2448.
- McDonald JW, Levine JM, Qu Y: Multiple classes of the oligodendrocyte lineage are highly vulnerable to excitotoxicity. Neuroreport 1998;9:2757–2762.
- Follett PL, Rosenberg PA, Volpe JJ, Jensen FE: NBQX attenuates excitotoxic injury in developing white matter. J Neurosci 2000;20:9235–9241.
- Jelinski SE, Yager JY, Juurlink BH: Preferential injury of oligodendroblasts by a short hypoxic-ischemic insult. Brain Res 1999;815:150–153.
- Puka-Sundvall M, Gajkowska B, Cholewinski M, Blogren K, Lazarewicz JW, Hagberg H: Subcellular distribution of calcium and ultrastructural changes after cerebral hypoxia-ischemia in immature rats. Dev Brain Res 2000;123:31–41.
- Rice JE, Vannucci RC, Brierley JB: The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 1981;9:131–141.
- Vannucci SJ, Seaman LB, Vannucci RC: Effects of hypoxia-ischemia on GLUT1 and GLUT3 glucose transporters in immature rat brain. J Cereb Blood Flow Metab 1996;16:77–81.
- Levison SW, Rothstein RP, Brazel CY, Young GM, Albrecht PJ: Selective apoptosis within the rat subependymal zone: A plausible mechanism for determining which lineages develop from neural stem cells. Dev Neurosci 2000;22:106–115.
- Stallcup WB, Beasley L: Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan. J Neurosci 1987;7:2737–2744.
- Martin LJ: Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res Bull 1998;46:281–309.
- Ferrer I, Tortosa A, Macaya A, Sierra A, Moreno D, Munell F, Blanco R, Squier W: Evidence of nuclear DNA fragmentation following hypoxia-ischemia in the infant rat brain, and transient forebrain ischemia in the adult gerbil. Brain Pathol 1994;4:115–122.
- Towfighi J, Zec N, Yager J, Housman C, Vannucci RC: Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: A light microscopic study. Acta Neuropathol 1995;90:375–386.
Levison SW, Rothstein RP, Romanko MJ, Snyder MJ, Meyers RL, Vannucci SJ: Hypoxia/ischemia depletes the perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells, submitted.
- Cheepsunthorn P, Palmer C, Menzies S, Roberts RL, Connor JR: Hypoxic/ischemic insult alters ferritin expression and myelination in neonatal rat brains. J Comp Neurol 2001;431:382–396.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.