Figure 2.

FHM1 mutant mice show accelerated lesion growth on MRI during hyperacute stroke. a) ADC lesion (i.e., ischemic core with restricted water diffusion, purple) was larger on diffusion-weighted MR images in S218L (left panel) and R192Q (right panel) mutants compared to WT during the hyperacute phase after fMCAO. b) ADC lesion volumes shown as a function of time after fMCAO were 40–50% larger in S218L and R192Q HOM compared to WT as early as 30 minutes after fMCAO suggesting faster growth of ischemic core (p=0.019 and p=0.018, respectively). The difference remained significant at 60 minutes. Vertical and horizontal error bars reflect the standard errors for total ADC lesion volume and timing of MRI scans, respectively. c) Thirty minutes after stroke onset, enlarged ADC lesion volumes in S218L HOM and R192Q HOM were primarily due to more severe cortical involvement (p=0.015 and p=0.023, respectively), although S218L HOM mutants showed hyperacute ADC changes in the hippocampus and thalamus as well (P=0.018 and P=0.117, respectively). Of note, the average regional ADC values in the center of ischemic core did not significantly differ between FHM1 mutants and their WT controls, suggesting that cytotoxic cell swelling is complete in ischemic core in all groups (60±7% vs. 56±6% in R192Q WT and HOM, and 57±5% vs. 57±6% of contralateral hemisphere in S218L WT and HOM, respectively, 60 minutes after stroke onset). *p<0.05 vs. WT.