Effect of Ultramicro Superparamagnetic Iron Oxide Nanoparticles on Cerebral Infarction in Mice.

To investigate the effect of Feraheme (ferumoxytol) intravenous injection on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. We randomly divided 30 CS7BL6J mice into sham operated group, normal saline control group, and Feraheme group with 10 mice in each group. The model of permanent occlusion of right middle cerebral artery was made via the modified suture method in the normal saline control group and the Feraheme group. After 24 h of establishment the model, the tail vein was injected with 18 mg/kg Feraheme in the sham operation group and Feraheme group, and the normal saline control group was injected with an equal volume of normal saline. Neurobehavioral scores were obtained 24 h (before injection of Feraheme or normal saline) and 48 h (before MRI) after the model was established. The volume of cerebral infarction was calculated according to T2 weighted imaging. Orbital blood was collected after nodal scanning to detect serum TNF-α, IL-1ß, and IL-6 levels. Then, the brain tissues of mice were killed for HE staining and IBAL immunohistochemical staining. No significant differences in cerebral infarction volume and neurological function were observed between the normal saline control group and Feraheme group. The levels of TNF-α, IL-1ß and IL-6 in the normal saline control group and Feraheme group were significantly higher than those in the sham operation group (P < 0.05), but there were no significant differences between the normal saline control group and Feraheme group. We showed that intravenous injection of 18 mg/kg Feraheme 24 h after cerebral ischemia does not affect the infarct volume and inflammatory response, suggesting that the dose of Feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

Montelukast inhibits oxidized low-density lipoproteins (ox-LDL) induced vascular endothelial attachment: An implication for the treatment of atherosclerosis.

Recruitment of monocytes to endothelial cells is important during early stages of atherosclerosis development, which is activated in response to a number of inflammatory stimuli, including oxidized low-density lipoprotein (ox-LDL). Montelukast is a licensed drug approved by the Food and Drug Administration (FDA) and clinically used for the treatment of asthma by reducing the eosinophilic inflammation in the airway. Little information regarding the effects of Montelukast on endothelial inflammation has been reported before. In the current study, we found that Montelukast markedly reduced ox-LDL-induced monocyte adhesion to human umbilical vein endothelial cells. In addition, the inhibitory mechanism of Montelukast was associated with suppression of adhesion molecule expression, including VCAM-1 and E-selectin. Mechanistically, ERK5 mediated expression of the transcriptional factor KLF2 was found to be involved in the anti-inflammation effects of Montelukast against ox-LDL induced endothelial inflammation. Results indicate that Montelukast plays a protective role in the early stages of atherosclerosis.