Gray Matter Oligodendrocyte Progenitors and Neurons Die Caspase-3 Mediated Deaths Subsequent to Mild Perinatal Hypoxic/Ischemic Insults

• Published in: Developmental neuroscience Vol. 27; no. 2-4; pp. 149 - 159
• Main Authors: Rothstein, Raymond P., Levison, Steven W.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.03.2005
• Subjects: Animals; Animals, Newborn; Apoptosis - physiology; Brain - blood supply; Brain - pathology; Carotid Arteries - surgery; Caspase 3; Caspases - metabolism; Disease Models, Animal; Female; Hypoxia-Ischemia, Brain - pathology; In Situ Nick-End Labeling; Ligation; Male; Neurons - pathology; Oligodendroglia - pathology; Original Paper; Rats; Stem Cells - pathology; Choroid plexus; Stroke; Cell death; Subventricular zone; Apoptosis
• ISBN: 9783805579902; 380557990X
• ISSN: 0378-5866; 1421-9859
• DOI: 10.1159/000085987

With significant improvements in neonatal care, fewer infants sustain severe injury as a consequence of hypoxia/ischemia (H/I). However, the majority of experimental studies have inflicted moderate to severe injuries, or they have assessed damage to the caudal forebrain; therefore, to better understand how a mild H/I episode affects the structures and cells of the rostral forebrain, we assessed the relative vulnerabilities of cells in the neocortex, striatum, corpus callosum, choroid plexus and subventricular zone (SVZ). To inflict mild H/I injury, the right common carotid artery was ligated followed by 1 h of hypoxia (8% O 2 ) at 37°C. Regional vulnerabilities were assessed using TUNEL, active caspase-3 and hematoxylin and eosin staining at 24 and 48 h of recovery. Scattered columns of cell death were observed in the neocortex with deep-layer neurons more vulnerable than more superficial neurons. The majority of these dying neurons appeared to be dying apoptotic rather than necrotic deaths. In addition, approximately 1/3 of the apoptotic cells in the neocortex were O4+ oligodendrocyte progenitors. We also observed a decrease in NG2 staining within the affected regions of the forebrain. By contrast, active caspase-3+/S-100β+ astrocytes were not observed. Neurons and O4+ oligodendrocyte progenitors also died apoptotic deaths within the striatum. The lining cells of the choroid plexus also sustained damage. Elevated numbers of apoptotic cells were observed in the most lateral region of the SVZ and some of these dying cells were O4+. The most novel finding of this study, that oligodendrocyte progenitors in the gray matter are damaged and eliminated as a consequence of perinatal H/I, provides new insights into the histopathology and neurological deficits observed in infants who sustain mild H/I brain injuries.