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.
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