Cholesterol crystal embolization in rat brain: a model for atheroembolic cerebral infarction.

Steiner, Th.; Rail, David; Fc, Rose

doi:10.1161/01.str.11.2.184

Cited by 16 publications

(10 citation statements)

References 14 publications

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“…Most observed, however, were much smaller, 20-50 /x, and irregular shape, due to fragmentation. This agrees with recent estimates by Steiner et al 33 Vessels found to be occluded by atheroembolic material (those with at least one visible cholesterol cleft in an occlusive mass) ranged in diameter from 10 /x in small parenchymal vessels to over 800 /x in some leptomeningeal vessels. These measurements excluded major vessels contributing to, of and branching from the Circle of Willis.…”

Section: Resultssupporting

confidence: 92%

“…There is strong evidence that cholesterol crystals can create obstructions within appropriately sized arteries but are relatively nonreactive, and if small enough are removed from the lesion site by macrophages. 32,33 There is also evidence that there are components of atheroma which are thrombogenic and/or inflammatory. 23,26 These latter sequelae may contribute more to morbidity and death, in that they may augment and stabilize an embolic mass which may otherwise have been pathologically benign.…”

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confidence: 99%

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Cerebral atheroembolism. An animal model.

Jeynes¹,

Warren²

1982

Stroke

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SUMMARY Human atheromatous material was injected into the cerebral vasculature of anaesthetized rabbits via the left common carotid artery. The lethality of varying dosages was determined and the distribution and general character of occlusive vascular lesions which developed were analyzed by light and transmission electron microscopy. It was found that a dose exceeding 55 mg of the atheramatous material (125 mg/nil saline) was lethal in New Zealand white male rabbits weighing between 3 and 5 kg. In nonsurviving animals, parts of the Circle of Willis and usually one or more of its major tributaries were occluded. Some surviving animals exhibited signs of neurologic deficit evidenced by motor dysfunction. Occlusive vascular lesions found in surviving animals were predominently localized in ipselateral cortical and subcortical vessels within the distribution territory of the middle cerebral artery. The character of occlusive lesions showed strong evidence of thrombosis. These results demonstrated that this experimental system may be useful as a model for the study of blood-atheroembolic vascular reactions, cerebral infarction development and the testing of agents potentially prophylactic against the development or stabilization of occlusive lesions. Stroke, Vol 13, No 3, 1982

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Section: Resultssupporting

confidence: 92%

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confidence: 99%

Cerebral atheroembolism. An animal model.

Jeynes¹,

Warren²

1982

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“…USP cholesterol crystals are chemically similar to those in human atherosclerotic plaque, but in our model, the size and number injected were titrated to create injury with rare neuronal infarction. Cholesterol crystals in human plaque exist in a range of sizes that include lengths both less and greater than 100 m. 11 The emboli injected create a "shower" of crystals, whereas the emboli in humans occur at a low rate and accumulate over time. The importance of this is unknown, but our attempt at repeated embolic episodes caused cognitive impairment whereas single injections of the same total number of crystals did not.…”

Section: Discussionmentioning

confidence: 99%

“…For the current study, we used USP nonesterified cholesterol crystals, size 60 to 100 m. These slender crystals are similar to those seen as cholesterol clefts in the plaque necrotic core, where they can account for up to one third of the plaque by weight. 11 The extent of brain injury caused by cholesterol embolization was examined in young adult rats. Both young adult and middle-aged rats underwent behavioral testing to determine whether the cognitive decline in rats manifested in advanced age 12 could be produced prematurely by microembolization.…”

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confidence: 99%

Microemboli Composed of Cholesterol Crystals Disrupt the Blood-Brain Barrier and Reduce Cognition

Rapp

Pan

Neumann

et al. 2008

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Background and Purpose-Microemboli occur frequently in patients with asymptomatic carotid atherosclerosis. In other vascular beds, microemboli are known to initiate an inflammatory response, causing organ dysfunction. In the current study, we investigated whether emboli composed of cholesterol crystals, a component of human atherosclerotic plaque, could also cause inflammation and brain dysfunction demonstrated by cognitive impairment. Methods-Cholesterol crystals of 60 to 100 m were injected via the rat internal carotid artery. T2-weighted magnetic resonance imaging was conducted after 3 days to estimate infarct volume. Brains were examined for matrix metalloproteinase activation at 24 hours and for albumin leakage and microglia and astrocyte activation at 4 days and 1, 2, and 4 weeks after embolization. To determine changes in cognition, behavioral tests including open field, motor learning, and Barnes Maze tests were conducted on young adult and middle-aged rats 4 weeks after either a single injection or after repeated, bilateral injections given at an interval of 2 weeks. Results-Matrix metalloproteinase activation was detected in 50% of the animals examined. Perivascular albumin staining was found at 4 days but rarely persisted beyond 1 week. Activation of microglia and astrocytes occurred in all animals and persisted for up to 8 weeks. Cognitive impairment was observed in middle-aged rats after repeated, bilateral injections but not after single injections. In these animals, areas of inflammation were small and scattered but often involved the striatum and hippocampus. Conclusions-Cholesterol embolization caused an inflammatory response in the brain with persistent activation of microglia and astrocytes and led to cognitive impairment after repeated injections in middle-aged animals with only small foci of neural injury. These data indicate that microembolization causes inflammation and that minimal neuronal injury can cause cognitive impairment in older animals.

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“…Vessel occlusions were seen with thrombus injection, but not after the injection of cholesterol emboli, which may reduce flow by transient vessel constriction around the crystals. 20 Both embolic materials caused foci of injury more frequently than infarction. These were characterized by albumin leakage and focal activation of microglia.…”

Section: Discussionmentioning

confidence: 99%