Thrombus fragments are globular and likely to completely obstruct terminal vessels. In contrast, previous work with “”atheroemboli”" of needle-like cholesterol crystals rarely cause occlusions or infarctions instead creating small foci of inflammation. In this work, we asked if microthrombi would occlude terminal vessels land create lacunar type infarctions in the PSI-7977 order subcortical tissues of the rat brain where, as in human brain, collateral flow is limited relative to the cortex.
Methods:
Three treatment groups of adult male Sprague-Dawley rats were studied. All groups underwent general anesthesia with monitoring of temperature and blood pressure during cannulation of the right internal carotid artery. In the group embolized with thrombus fragments (n = 12), animals had injections of 300 fragments of thrombus size 60 to 100 microns, the cholesterol group (n = 6) had injections of 300 cholesterol crystals of similar size, and the control group (n = 4) had injections of saline. Brains were harvested at 4 days with perfusion fixation and were examined by immunohistochemical staining for breaks in the blood brain barrier (BBB) (albumin), microglial activation (CD11b), astrocyte activation (GFAP), and infarction (loss of NeuN staining). Size and location of the
areas Selleck AZD1080 of injury and infarction were recorded.
Results. Clot fragments caused discreet infarcts in 10/12 animals that were 0.1-1.7 mm in diameter and coincided with activation of microglia and astrocytes.
In some areas, necrosis was already underway at this selleck chemicals early time point. Consistent with our previous work, the infarcts caused by cholesterol crystals were smaller (P = .014). Foci of BBB disruption and microglial activation were distributed throughout the brain whereas areas of infarction were found almost exclusively in subcortical tissues (P = .029).
Conclusions. Injecting microthrombi reproducibly caused areas of necrosis resembling lacunar type infarctions. These were primarily located in the striatum and thalamus presumably because these areas lack the branching, collateral network seen in the cortex. In addition, these data give further evidence that the extent of brain injury from emboli depends upon composition and shape as well as size.”
“Two hypotheses concerning cerebellar function and predictive behavior are the sensory prediction hypothesis and the timing hypothesis. The former postulates that the cerebellum is critical in generating expectancies regarding forthcoming sensory information. The latter postulates that this structure is critical in generating expectancies that are precisely timed; for example, the expected duration of an event or the time between events. As such, the timing hypothesis constitutes a more specific form of prediction. The present experiment contrasted these two hypotheses by examining the mismatch negativity (MMN) response in patients with cerebellar cortical atrophy and matched controls.