RT Journal Article
SR Electronic
T1 Delayed Expression of Osteopontin after Focal Stroke in the Rat
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2075
OP 2083
DO 10.1523/JNEUROSCI.18-06-02075.1998
VO 18
IS 6
A1 Xinkang Wang
A1 Calvert Louden
A1 Tian-Li Yue
A1 Julie A. Ellison
A1 Frank C. Barone
A1 Henk A. Solleveld
A1 Giora Z. Feuerstein
YR 1998
UL http://www.jneurosci.org/content/18/6/2075.abstract
AB Focal brain ischemia induces inflammation, extracellular matrix remodeling, gliosis, and neovascularization. Osteopontin (OPN) is a secreted glycoprotein that has been implicated in vascular injury by promoting cell adhesion, migration, and chemotaxis. To investigate the possible involvement of OPN in brain matrix remodeling after focal stroke, we examined the expression of OPN in ischemic cortex after permanent or temporary occlusion of the middle cerebral artery (MCAO) of the rat. OPN mRNA and protein levels in nonischemic cortex were not detected consistently, although significant induction of OPN was observed in the ischemic cortex. OPN mRNA increased 3.5-fold at 12 hr and reached peak levels 5 d (49.5-fold; p < 0.001) after permanent MCAO. The profile of OPN mRNA induction after transient MCAO (160 min) with reperfusion was essentially the same as that of permanent MCAO. In situ hybridization and immunohistochemical studies demonstrated strong induction of OPN in the ischemic cortex, which was localized primarily in a subset of ED-1-positive macrophages that accumulated in the ischemic zone. Moreover, OPN immunoreactivity was detected in the matrix of ischemic brain, suggesting a functional role of the newly deposited matrix protein in cell–matrix interactions and remodeling. Indeed, using a modified Boyden chamber, we demonstrated a dose-dependent chemotactic activity of OPN in C6 astroglia cells and normal human astrocytes. Taken together, these data suggest that the upregulation of OPN after focal brain ischemia may play a role in cellular (glia, macrophage) migration/activation and matrix remodeling that provides for new matrix–cell interaction.