Angiography of the Left Posterior Circulation of the Brain

<p>Angiography (sagittal view) demonstrates complete occlusion of the left vertebral artery (black arrow).</p

Trans-Esophageal Echocardiogram (TEE)

<p>TEE view of significant mitral stenosis (thickening of the mitral valve leaflets with doming of the anterior leaflet) with severe spontaneous echo contrast (white arrow).</p

Angiography of the Left Anterior Circulation of the Brain—Following Thrombolysis

<p>Antero-posterior view demonstrates a renewed flow in the left internal carotid artery and the left hemisphere.</p

Magnetic Resonance Angiography (MRA)

<p>MRA shows the left MCA occluded by a thrombus at its origin (white arrow). This technique uses MR to demonstrate blood vessels within the central nervous system.</p

Diffusion-Weighted Imaging (DWI) of the Brain

<p>Diffusion defect indicating irreversible left hemispheric ischemic damage in the area controlling right hand and leg function.</p

Perfusion-Weighted Imaging (PWI) of the Brain

<p>Perfusion amplified signal mismatch (compared to <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030233#pmed-0030233-g001" target="_blank">Figure 1</a>), indicating an ischemic area with abnormal function, but no cellular death, salvageable by reperfusion. </p

Angiography of the Left Anterior Circulation of the Brain

<p>Angiography shows the left internal carotid artery with an occlusion of one of its main branches, the left MCA (arrow shows origin occluded by a thrombus).</p

Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization

<div><p>Recent evidence that excessive lipid accumulation can decrease cellular levels of autophagy and that autophagy regulates immune responsiveness suggested that impaired macrophage autophagy may promote the increased innate immune activation that underlies obesity. Primary bone marrow-derived macrophages (BMDM) and peritoneal macrophages from high-fat diet (HFD)-fed mice had decreased levels of autophagic flux indicating a generalized impairment of macrophage autophagy in obese mice. To assess the effects of decreased macrophage autophagy on inflammation, mice with a <i>Lyz2</i>-<i>Cre</i>-mediated knockout of <i>Atg5</i> in macrophages were fed a HFD and treated with low-dose lipopolysaccharide (LPS). Knockout mice developed systemic and hepatic inflammation with HFD feeding and LPS. This effect was liver specific as knockout mice did not have increased adipose tissue inflammation. The mechanism by which the loss of autophagy promoted inflammation was through the regulation of macrophage polarization. BMDM and Kupffer cells from knockout mice exhibited abnormalities in polarization with both increased proinflammatory M1 and decreased anti-inflammatory M2 polarization as determined by measures of genes and proteins. The heightened hepatic inflammatory response in HFD-fed, LPS-treated knockout mice led to liver injury without affecting steatosis. These findings demonstrate that autophagy has a critical regulatory function in macrophage polarization that downregulates inflammation. Defects in macrophage autophagy may underlie inflammatory disease states such as the decrease in macrophage autophagy with obesity that leads to hepatic inflammation and the progression to liver injury.</p></div