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
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
Steven W. Levison, PhD
Department of Neuroscience and Anatomy, H109
Pennsylvania State University College of Medicine, PO Box 850
Hershey, PA 17033 (USA)
Tel. +1 717 531 8650, Fax +1 717 531 0714, E-Mail Slevison@psu.edu
Received: Received: April 20, 2001
Accepted: May 7, 2001
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 0, Number of References : 19
Vol. 23, No. 3, Year 2001 (Cover Date: May-June 2001 (Released October 2001))
Journal Editor: A.T. Campagnoni, Los Angeles, Calif.
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/journals/dne