Dynamic changes of inflammation and apoptosis in cerebral ischemia-reperfusion injury in mice investigated by ferumoxytol-enhanced magnetic resonance imaging

The inflammatory response and apoptosis are key factors in cerebral ischemia-reperfusion injury. The severity of the inflammatory reaction and apoptosis has an important impact on the prognosis of stroke. The ultrasmall superparamagnetic iron oxide particle has provided an effective magnetic resonance molecular imaging method for dynamic observation of the cell infiltration process in vivo. The aims of the present study were to investigate the inflammatory response of cerebral ischemia-reperfusion injury in mice using ferumoxytol-enhanced magnetic resonance imaging, and to observe the dynamic changes of inflammatory response and apoptosis. In the present study a C57BL/6n mouse cerebral ischemia-reperfusion model was established by blocking the right middle cerebral artery with an occluding suture. Subsequently, the mice were injected with ferumoxytol via the tail vein, and magnetic resonance scanning was performed at corresponding time points to observe the signal changes. Furthermore, blood samples were used to measure the level of serum inflammatory factors, and histological staining was performed to assess the number of iron-swallowing microglial cells and apoptotic cells. The present results suggested that there was no significant difference in the serum inflammatory factors tumor necrosis factor-α and interleukin 1β between the middle cerebral artery occlusion (MCAO) and MCAO + ferumoxytol groups injected with ferumoxytol and physiological saline. The lowest signal ratio in the negative enhancement region was decreased 24 h after reperfusion in mice injected with ferumoxytol. The proportion of iron-swallowing microglial cells and TUNEL-positive cells were the highest at 24 h after reperfusion, and decreased gradually at 48 and 72 h after reperfusion. Therefore, the present results indicated that ferumoxytol injection of 18 mg Fe/kg does not affect the inflammatory response in the acute phase of cerebral ischemia and reperfusion. Ferumoxytol-enhanced magnetic resonance imaging can be used as an effective means to monitor the inflammatory response in the acute phase of cerebral ischemia-reperfusion injury. Furthermore, it was found that activation of the inflammatory response and apoptosis in the acute stage of cerebral ischemia-reperfusion injury is consistent.