White matter injury in the immature brain: role of interleukin-18.
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.
Hedtjärn
Maj
M
Perinatal Center, Department of Physiology, Göteborg University, Box 432, 405 30 Göteborg, Sweden. maj.hedtjarn@fysiologi.gu.se
Mallard
Carina
C
Arvidsson
Pernilla
P
Hagberg
Henrik
H
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism
D020382:Interleukin-18; D004676:Myelin Basic Protein