MICROVASCULAR AND NEURONAL CONSEQUENCES OF COMMON CAROTID-ARTERY THROMBOSIS AND PLATELET EMBOLIZATION IN RATS

The microvascular and neuronal consequences of nonocclusive common carotid artery (CCA) thrombosis were documented in rats. Thrombosis of the CCA was produced by a rose bengal-mediated photochemical insult and regional patterns of blood-brain barrier (BBB) disruption were documented by horseradish peroxidase (HRP) histochemistry at 15 min (n = 12), 4 h (n = 3), 1 day (n = 5) or 7 days (n = 5) after vascular injury. At 15 min and 4 h after thrombosis, multiple foci of BBB disruption were present throughout the thrombosed hemisphere; protein leakage was occasionally detected contralaterally. Extravasated HRP was associated with well-perfused arterioles and arterioles containing luminal platelet aggregates at different stages of degranulation. Evidence for local platelet adhesion and aggregation or endothelial disruption at these sites was not detected. However, HRP-containing endothelial plasmalemmal vesicles were present at leaky sites. Variable degrees of parenchymal injury were documented including dendritic and astrocytic swelling with neuronal necrosis. By 1 day after CCA thrombosis, the overall frequency of permeable sites, more commonly associated with luminal leukocytes and parenchymal necrosis, was reduced. At 7 days, vessels permeable to HRP were associated with tissue necrosis, reactive astrocytes and microglial infiltration. Arteriole wall thickening and leukocyte accumulation within arterioles and venules were also detected. Widespread platelet embolization leading to variable degrees of BBB disruption and tissue injury occurs after CCA thrombosis. Acute abnormalities in vascular permeability are thus hypothesized to play an important role in the acute pathogenesis of cerebrovascular thrombosis. Delayed leukocyte accumulation in this model of embolic infarction may represent a secondary insult to the injured brain.