Effect of intravenous feraheme on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion

Objective To investigate the effect of intravenous ultrafine superparamagnetic iron oxide nanoparticles feraheme (generic name: ferumoxytol) on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. Methods Thirty C57BL/6J mice were divided into sham operation group, saline control group, and feraheme group by the random number table (n=10 in each group). A permanent right middle cerebral artery occlusion model was induced by the modified suture method in the saline control group and the feraheme group, and no suture was inserted into the mice of the sham operation group. The intervention was performed by tail vein injection at 24 h after modeling. The sham operation group and the feraheme group were injected with 18 mg/kg feraheme, and the saline control group was injected with the same volume of normal saline. The neurobehavioral scores were conducted at 24 h (before the feraheme or saline injection) and 48 h (before the MRI exam) after modeling. MRI scans were performed at 48 h after modeling, and the cerebral infarction volume was calculated according to T2-weighted imaging. After the end of the scan, orbital blood was collected for the detection of serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels. Then, the mice were sacrificed and the brain tissue was taken for HE staining and Iba1 immunohistochemical staining. Results There were no significant differences in the infarct volume and neurological function score between the saline control group and the feraheme group. The serum levels of TNF-α, IL-1β, and IL-6 in the saline control group and the feraheme group were significantly higher than those in the sham operation group (P<0.05), but there was no significant difference between the saline control group and the feraheme group. Conclusion Intravenous injection of 18 mg/kg feraheme at 24 h after cerebral ischemia did not affect the infarct volume and inflammatory response, suggesting that this dose of feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia. Key words: Brain ischemia; Brain infarction; Ferrosoferric oxide; Inflammation; Microglia; Magnetic resonance imaging; Disease models, animal; Mice