INFLUX OF LEUKOCYTES AND PLATELETS IN AN EVOLVING BRAIN INFARCT (WISTAR RAT)

The results of several experimental studies of focal ischemia and anec dotal observations suggest that leukocytes may contribute to the injur y initiated by an arterial occlusion. The timing and the nature of leu kocyte responses in evolving brain infarcts (either human or experimen tal) are incompletely characterized. This is a study of experimental b rain lesions in 96 Wistar rats that underwent occlusion of a large int racranial artery for variable intervals ranging between 30 minutes and 7 days. The experimental model, based on the occlusion of a middle ce rebral artery ostium via the insertion of a nylon monofilament through the external carotid artery, does not require opening the skull; ther efore, the inflammatory response is not influenced by the effects of c raniotomy and changes in intracranial pressure are only those induced by the ischemic lesion. All 96 animals having the same type of arteria l occlusion developed an ischemic brain lesion (limited to the territo ry of the corresponding artery) that evolved into an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by pannecro sis (infarct) approximately 60 hours later. In this study, leukocytes (in particular polymorphonuclear cells) were detected in the microvess els (capillaries and venules) of the ischemic hemisphere as early as 3 0 minutes after the arterial occlusion. Numbers of intravascular neutr ophils peaked at 12 hours, whereas intraparenchymal granulocytes were most numerous at 24 hours; a few granulocytes were visible in the brai n infarct as late as day 7. Circulating monocytes were first detected within the capillaries/venules of the ischemic area after 4 to 6 hours . Platelet aggregates were more abundant in the arterial than the veno us side of the circulation, and luminal obstruction of arteries by pla telet aggregates became noticeable only 48 hours after the arterial oc clusion. Fibrin thrombi were conspicuous for their absence. These obse rvations provide the background for studies that will attempt to unrav el the relationship between the biological responses of leukocytes and neuronal necrosis secondary to focal ischemia.