Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion.
Early intervention after acute ischemic stroke is essential to minimize brain cell injury. Although reperfusion of the ischemic brain is the treatment of choice for acute stroke, reperfusion itself may cause additional injury. The inflammatory cascade, characterized in part by early leukocyte interaction with endothelium, may contribute to this additional injury to blood vessels and surrounding brain tissue, extending the area of infarction. The selectin family of adhesion molecules mediates the initial, rolling and tethering of leukocytes to endothelium. P-selectin is rapidly expressed on ischemic endothelium in the brain vasculature, and L-selectin is expressed on leukocytes. Blocking the selectin-mediated tethering step may limit the inflammatory component of reperfusion injury in the brain. Fucoidin (FCN), a competitive inhibitor of P- and L-selectin, has been reported to decrease leukocyte accumulation during reperfusion of other organs. The effect of both leukocyte and endothelial selectin inhibition after cerebral ischemia and reperfusion has not been previously examined. The purpose of this study was to determine the effects of selectin adhesion molecule blockade on cerebral infarction size and neurological function after middle cerebral artery occlusion and reperfusion (MCAO-R) in the rat. MCAO was induced using the filament method. All animals were subjected to 4 h of MCAO and 24 h of reperfusion. After 24 h, brains were analyzed for size of infarction. Neurological function was assessed during stroke and 24 h after reperfusion. Two groups were studied, an untreated control group (n = 9) and a group treated with the selectin inhibitor, fucoidin (25 mg kg(-1)) (n = 9). We found that selectin blockade significantly reduced cerebral infarction size by 50% (p < 0.05) and improved neurological function (p < 0.05). In addition, a trend toward decreased cerebral edema was demonstrated with selectin inhibition. These results indicate that treatment of the blood and the endothelium with a selectin anti-inflammatory agent is protective after focal stroke and reperfusion in the rat.
Ruehl
Mary L
ML
University of Arizona College of Nursing, USA.
Orozco
Jose A
JA
Stoker
Matthew B
MB
McDonagh
Paul F
PF
Coull
Bruce M
BM
Ritter
Leslie S
LS
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019087:Selectins / Q000097:blood* / Q000378:metabolism
D011134:Polysaccharides; D019087:Selectins; C007789:fucoidan