Do Microemboli Reach the Brain Penetrating Arteries?

Background. As they are "end arteries,'' microembolic obstruction of brain penetrating arteries would be expected to create ischemia. Yet the mammalian brain appears to have an impressive tolerance to experimental microembolization with ischemia occurring only after the injection of large numbers of particulates. Potential explanations could be that the majority of these particulates marginate along the pial vasculature or escape the cerebral circulation via arteriovenous (AV) fistulae. Methods. To test these theories, we first established the level of injury created by the injection of 20, 45, and 90 mm fluorescent microspheres in Sprague-Dawley rats. Brains were examined by immunohistochemistry for injury and for infarction. We then injected 1000 size 20 mm, 500 size 45 mu m, and 150 size 90 mu m and harvested the brains and lungs for assays of fluorescence. The location of microemboli within the brain was established by determining the percent of 20 and 45 mu m fluorescent microspheres entering the superficial versus deeper layers of the brain. The location of larger microemboli was established by 2T-MRI after injection of 60-100 mm microthrombi labeled with supraparamagnetic iron oxide (SPIO) particles. Results. With 20 mm microspheres there were no areas of injury or infarction after injection of 500 and rare areas of injury and no infarctions after injection of 1000 microspheres. With either 250 or 500 size 45 mm microspheres there were a few (<= 6) small areas of injury per animal with <= 2 areas of infarction. After injection, 93%-96% of injected microspheres remained in the brain. Approximately 40% of either fluorescent or SPIO labeled microthrombi were found on the brain surface. Conclusions. As in humans, the rat brain has an impressive tolerance to microemboli, although this clearly varies with emboli size and number. Wash out of particulates through AV connections is not a major factor in brain tolerance in this model. Approximately 40% of microemboli remain in the larger pial vasculature where the more extensive collateralization may limit their effects on distal perfusion. However, the remaining 60% enter penetrating arteries but few create ischemia. Published by Elsevier Inc.