In Vivo Brain Redox Imaging In Transgenic-Knockout Sickle Mice

BACKGROUND: Sickle RBCs generate excessive reactive oxygen species (ROS) due to increased HbS auto-oxidation and cell lysis. High plasma ROS lead to increased oxidative stress in the brain, where oxidative stress is linked with the etiology of a host of cerebral disorders. Noninvasive assessment of cerebral oxidative stress could be useful in understanding how ROS affects the brain in sickle cell disease. We examined a blood-brain barrier-permeable and stable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MCP), which is a paramagnetic T1-shortening MRI contrast agent in its oxidized state. MCP participates in cellular redox reactions (is reduced by free radicals, ubiquinols, ascorbate, glutathione (GSH), etc.) and once reduced, it loses its ability to generate MRI contrast (becomes diamagnetic). MCP is highly lipophilic, and enters the brain rapidly after intravenous infusion. The rate of loss of contrast within the brain tissue after intravenous infusion is related to tissue ROS load. We employed MCP to evaluate the cerebral ROS levels in transgenic-knockout sickle mice.