White matter injury in the immature brain: role of interleukin-18

• Published in: Neuroscience letters Vol. 373; no. 1; pp. 16 - 20
• Main Authors: Hedtjärn, Maj, Mallard, Carina, Arvidsson, Pernilla, Hagberg, Henrik
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03.01.2005; Elsevier
• Subjects: Animals; Animals, Newborn; Astrocytes - metabolism; Biological and medical sciences; Cytokine; Female; Fundamental and applied biological sciences. Psychology; Hypoxia-ischemia; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - pathology; Immunohistochemistry; Inflammation; Injury; Interleukin-18 - deficiency; Interleukin-18 - metabolism; Male; Mice; Mice, Knockout; Microglia - metabolism; Myelin Basic Protein - metabolism; Neonatal; Vertebrates: nervous system and sense organs; White matter; Neonatal; Inflammation; White matter; Injury; Hypoxia-ischemia; Cytokine; Oxygen; Central nervous system; Cardiovascular disease; Encephalon; Interleukin 18; Ischemia; Hypoxia; Lesion
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2004.09.062

Inflammation is likely to be important in the pathophysiology of white matter damage in the immature brain. In order to investigate the involvement of interleukin (IL)-18, we subjected 9-day-old IL-18-deficient and wild-type (WT) mice to hypoxia-ischemia (HI) (unilateral carotid ligation and exposure to 10% oxygen) and white matter injury was evaluated after 3 days by immunostaining for myelin basic protein (MBP) and neurofilament (NF). The immunoreactivity of MBP was significantly higher by 92, 49 and 21%, respectively, in subcortical white matter, striatum and thalamus in IL-18-deficient mice versus WT mice following HI. Similarly, there was a more pronounced immunoreactivity of NF by 78% in the subcortical white matter in IL-18 KO versus WT mice. IL-18 was expressed by astrocytes and microglia, whereas the IL-18 receptor was mainly found in astrocytes localized in and around the subventricular white matter. Taken together, these results indicate that release of IL-18 may play an important role in the development of white matter injury in the neonatal brain.