Transgenic mice expressing human copper–zinc superoxide dismutase exhibit attenuated apparent diffusion coefficient reduction during reperfusion following focal cerebral ischemia

Since ADC reduction reflects intracellular edema which is an early indicator of ischemic cellular metabolic stress, we hypothesized that a decrease in ADC as determined by diffusion weighted MR imaging could be attenuated by SOD expression in transgenic mice during reperfusion following focal cerebral ischemia. Diffusion weighted imaging (DWI) was performed to evaluate apparent diffusion coefficient (ADC) reduction by constructing ADC maps with a color scale to localize ADC change in transgenic (Tg) mice expressing human CuZn superoxide dismutase (SOD) and wild type (Wt) mice during 1 h middle cerebral artery occlusion (MCAO) and 1 h reperfusion. Heat shock protein (hsp) 70-kDa mRNA analysis was evaluated as a marker of sublethal cell stress by in situ hybridization after 4 h reperfusion for comparison with Nissl staining of adjacent sections to assess infarction. Sequential ADC maps were prepared in Tg mice with sufficient temporal and spatial resolution to permit comparison with Wt mice. Tg mice showed substantial recovery of the ADC lesion after reperfusion, while Wt mice showed no recovery. There was no difference between Tg and Wt mice in the size or distribution of the ADC lesion during ischemia. The area with strong expression of hsp70 mRNA in the ischemic hemisphere was substantially larger in the Tg mice. Nissl staining showed less damage of brain tissue in Tg mice than Wt mice especially in the cortex after 4 h reperfusion following 1 h MCAO. Results demonstrate that antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h MCAO. Hsp70 could be one of the proteins that mediates protection by SOD against oxidative stress.