Upregulation of intercellular adhesion molecule 1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex.
The expression of intercellular adhesion molecule 1 (ICAM-1) was studied in rat focal ischemic cortex. A significant increase in ICAM-1 mRNA expression in the ischemic cortex over levels in contralateral (nonischemic) site was observed by means of Northern blot analysis following either permanent or temporary occlusion with reperfusion of the middle cerebral artery (PMCAO or MCAO with reperfusion) in spontaneously hypertensive rats. In the ischemic cortex, levels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, n = 3, P < 0.05), peaked at 6 to 12 h (6.0-fold, P < 0.01) and remained elevated up to 5 days (2.5-fold, P < 0.05) after PMCAO. The profile of ICAM-1 mRNA expression in the ischemic cortex following MCAO with reperfusion was similar to that following PMCAO, except that ICAM-1 mRNA was significantly increased as early as 1 h (6.3-fold, n = 3, P < 0.05) and then gradually reached a peak at 12 h (12-fold, P < 0.01) after reperfusion. ICAM-1 mRNA expression in ischemic cortex following PMCAO was significantly greater in hypertensive rats than in two normotensive rat strains. Immunostaining using anti-ICAM-1 antibodies indicated that upregulated ICAM-1 expression was localized to endothelial cells of intraparenchymal blood vessels in the ischemic but not contralateral cortex. The data suggest that an upregulation of ICAM-1 mRNA and protein on brain capillary endothelium may play an important role in leukocyte migration into ischemic brain tissue.
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
X
X
Wang
A L
AL
Siren
Y
Y
Liu
T L
TL
Yue
F C
FC
Barone
G Z
GZ
Feuerstein
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002536:Cerebral Arteries / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000378:metabolism*; D007839:Functional Laterality; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013045:Species Specificity
D017931:DNA Primers; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1