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

The microvascular and neuronal consequences of nonocclusive common car otid artery (CCA) thrombosis were documented in rats. Thrombosis of th e CCA was produced by a rose bengal-mediated photochemical insult and regional patterns of blood-brain barrier (BBB) disruption were documen ted 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. A t 15 min and 4 h after thrombosis, multiple foci of BBB disruption wer e present throughout the thrombosed hemisphere; protein leakage was oc casionally detected contralaterally. Extravasated HRP was associated w ith well-perfused arterioles and arterioles containing luminal platele t aggregates at different stages of degranulation. Evidence for local platelet adhesion and aggregation or endothelial disruption at these s ites was not detected. However, HRP-containing endothelial plasmalemma l vesicles were present at leaky sites. Variable degrees of parenchyma l injury were documented including dendritic and astrocytic swelling w ith neuronal necrosis. By 1 day after CCA thrombosis, the overall freq uency of permeable sites, more commonly associated with luminal leukoc ytes and parenchymal necrosis, was reduced. At 7 days, vessels permeab le to HRP were associated with tissue necrosis, reactive astrocytes an d microglial infiltration. Arteriole wall thickening and leukocyte acc umulation within arterioles and venules were also detected. Widespread platelet embolization leading to variable degrees of BBB disruption a nd tissue injury occurs after CCA thrombosis. Acute abnormalities in v ascular permeability are thus hypothesized to play an important role i n the acute pathogenesis of cerebrovascular thrombosis. Delayed leukoc yte accumulation in this model of embolic infarction may represent a s econdary insult to the injured brain.