In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration

Experimental timeline and [11C]MHED PET. a At least 1 week after baseline PET scans, ten adult rhesus macaques underwent systemic administration of 6-OHDA (50？mg/kg i.v.). At 24？h after 6-OHDA, animals were blindly, randomly assigned to either daily oral dosing of placebo (n？=？5) or pioglitazone (n？=？5; 5？mg/kg). b Cardiac distribution volume (DV) maps of MHED uptake at baseline, 1, and 12 weeks after 6-OHDA in representative placebo- and pioglitazone-treated monkeys (apex of heart at center, base of left ventricle at edge). Letters indicate region orientation (S septal, I inferior, L lateral, A anterior). Increased recovery of MHED uptake from 1 week to 12 weeks after 6-OHDA is evident in the pioglitazone-treated monkey, compared to placebo. Note that each animal has a unique color scale (units: DV). c Treatment group MHED uptake (mean？±？SE) in the cardiac left ventricle in three select levels from base to apex and across regions. Treatment？×？Region？×？Level ANOVA analysis revealed a significant difference at 12 weeks after neurointoxication (F(35, 280)？=？2.10, p？<？0.034, ηp2？=？0.21) and no significant difference at baseline (F(35, 280)？=？0.70, p？>？0.711, ηp2？=？0.081) or 1 week (F(35, 280)？=？0.78, p？>？0.510, ηp2？=？0.089). d 3D surface plots of group mean MHED uptake in the cardiac left ventricle at baseline, 1, and 12 weeks after 6-OHDA in the two groups across left ventricle regions and levels. The x-axis represents eight regions starting with septal and progressing though anterior, lateral, and inferior. The y-axis represents radioligand uptake in six levels of the left ventricle descending from base to apex. z-axis plot height and corresponding color scale represent values of MHED uptake (DV) at each anatomical area. Polynomial trend analysis did not reach a significant difference based on treatment [Treatment？×？Region (quadratic)？×？Level (linear): 33.24%, p？>？0.084, ηp2？=？0.327]. Simple interaction tests evaluating plot shape independently for each treatment confirmed distinct trends in the Region？×？Level shape (pioglitazone, quadratic？×？linear: 67.92%, p？<？0.019; placebo, cubic？×？linear: 26.61%, p？<？0.004)