Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.

Measurement of vessel stenosis by using ultrasonography or angiography remains the principal method for determining the severity of carotid atherosclerosis and the need for endarterectomy. The ipsilateral stroke rate, however--even in patients with severely stenotic vessels--is relatively low, which suggests that the amount of luminal narrowing may not represent the optimal means of assessing clinical risk. As a result, some patients may undergo unnecessary surgery. Improved imaging techniques are, therefore, needed to enable reliable identification of high-risk plaques that lead to cerebrovascular events. High-spatial-resolution magnetic resonance (MR) imaging has been described as one promising modality for this purpose, because the technique allows direct visualization of diseased vessel wall and can be used to characterize the morphology of individual atherosclerotic carotid plaques. The purpose of this report is to review the current state of carotid plaque MR imaging and the use of carotid MR to evaluate plaque morphology and composition.

Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function. Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two. Thus, the bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker.

Background and Purpose-MRI is able to quantify carotid plaque size and composition with good accuracy and reproducibility and provides an opportunity to prospectively examine the relationship between plaque features and subsequent cerebrovascular events. We tested the hypothesis that the characteristics of carotid plaque, as assessed by MRI, are possible predictors of future ipsilateral cerebrovascular events. Methods-A total of 154 consecutive subjects who initially had an asymptomatic 50% to 79% carotid stenosis by ultrasound with Ն12 months of follow-up were included in this study. Multicontrast-weighted carotid MRIs were performed at baseline, and participants were followed clinically every 3 months to identify symptoms of cerebrovascular events. Results-Over a mean follow-up period of 38.2 months, 12 carotid cerebrovascular events occurred ipsilateral to the index carotid artery. Cox regression analysis demonstrated a significant association between baseline MRI identification of the following plaque characteristics and subsequent symptoms during follow-up: presence of a thin or ruptured fibrous cap (hazard ratio, 17.0; PՅ0.001), intraplaque hemorrhage (hazard ratio, 5.2; Pϭ0.005), larger mean intraplaque hemorrhage area (hazard ratio for 10 mm 2 increase, 2.6; Pϭ0.006), larger maximum %lipid-rich/necrotic core (hazard ratio for 10% increase, 1.6; Pϭ0.004), and larger maximum wall thickness (hazard ratio for a 1-mm increase, 1.6; Pϭ0.008). Conclusions-Among patients who initially had an asymptomatic 50% to 79% carotid stenosis, arteries with thinned or ruptured fibrous caps, intraplaque hemorrhage, larger maximum %lipid-rich/necrotic cores, and larger maximum wall thickness by MRI were associated with the occurrence of subsequent cerebrovascular events. Findings from this prospective study provide a basis for larger multicenter studies to assess the risk of plaque features for subsequent ischemic events. (Stroke. 2006;37:818-823.)