Structural remodeling of gray matter astrocytes in the neonatal pig brain after hypoxia/ischemia

✍ Scribed by Susan M. Sullivan; S. Tracey Björkman; Stephanie M. Miller; Paul B. Colditz; David V. Pow

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 703 KB
• Volume: 58
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20911

✦ Synopsis

Abstract

Astrocytes play a vital role in the brain; their structural integrity and sustained function are essential for neuronal viability, especially after injury or insult. In this study, we have examined the response of astrocytes to hypoxia/ischemia (H/I), employing multiple methods (immunohistochemistry, iontophoretic cell injection, Golgi‐Kopsch staining, and D‐aspartate uptake) in a neonatal pig model of H/I. We have identified morphological changes in cortical gray matter astrocytes in response to H/I. Initial astrocytic changes were evident as early as 8 h post‐insult, before histological evidence for neuronal damage. By 72 h post‐insult, astrocytes exhibited significantly fewer processes that were shorter, thicker, and had abnormal terminal swellings, compared with astrocytes from control brains that exhibited a complex structure with multiple fine branching processes. Quantification and image analysis of astrocytes at 72 h post‐insult revealed significant decreases in the average astrocyte size, from 686 μm^2^ in controls to 401 μm^2^ in H/I brains. Sholl analysis revealed a significant decrease (>60%) in the complexity of astrocyte branching between 5 and 20 μm from the cell body. D‐Aspartate uptake studies revealed that the H/I insult resulted in impaired astrocyte function, with significantly reduced clearance of the glutamate analog, D‐aspartate. These results suggest that astrocytes may be involved in the pathophysiological events of H/I brain damage at a far earlier time point than first thought. Developing therapies that prevent or reverse these astrocytic changes may potentially improve neuronal survival and thus might be a useful strategy to minimize brain damage after an H/I insult. © 2009 Wiley‐Liss, Inc.