CD18-dependent leukocyte adherence and vascular injury in pig cerebral circulation after ischemia.
Recent accumulating evidence indicates that leukocytes contribute importantly to ischemic brain injury. Although large numbers of leukocytes are present in the ischemic territory of reperfused brain 24-48 h after the ischemic insult, little is known of the acute inflammatory response to cerebral ischemia, particularly regarding the time course and magnitude of leukocyte adherence to cerebrovascular endothelium and the functional consequences of such adherence. To study these issues, we developed an epifluorescence videomicroscopy system for observing and quantifying the dynamic behavior of rhodamine-labeled leukocytes in the cerebrovascular microcirculation. Anesthetized piglets equipped with closed cranial windows were used in these investigations. During the initial 2 h of reperfusion after 9 min of asphyxia (n = 6), a marked, progressive increase in adherent leukocytes was noted in cerebral postcapillary venules that was significantly greater in magnitude than that seen in nonasphyxic, time-matched controls (n = 8). A similar response was observed after complete global ischemia of 10 min duration. A significant increase in sodium fluorescein permeability was also measured at 2 h of reperfusion in asphyxic animals. Pretreating a separate asphyxic animal group (n = 7) with a monoclonal antibody to the leukocyte adhesion glycoprotein complex CD11/CD18 severely attenuated both leukocyte adherence and the increase in vascular permeability. These results provide evidence that adherent leukocytes contribute to disruption of endothelial integrity during early reperfusion after global ischemic insults, the inhibition of which may reduce the vasogenic edema that occurs early during reperfusion after birth asphyxia, stroke, and cardiac arrest.
Gidday
J M
JM
Department of Neurosurgery, St.Louis Children's Hospital, Washington University School of Medicine, Missouri 63110, USA.
Park
T S
TS
Gonzales
E R
ER
Beetsch
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002545:Brain Ischemia / Q000503:physiopathology*; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002199:Capillary Permeability; D002448:Cell Adhesion / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D013552:Swine
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens