%0 Journal Article
%T In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration
%A Bradley T. Christian
%A Carissa A. Boettcher
%A Catherine L. Gallagher
%A Colleen F. Moore
%A Helen N. Matsoff
%A Henry A. Resnikoff
%A James E. Holden
%A Jeanette M. Metzger
%A Kevin G. Brunner
%A Marina E. Emborg
%A Patrick J. Lao
%A R. Jerry Nickles
%A Rachel A. Fleddermann
%A Timothy A. Hacker
%A Timothy J. Kamp
%A Todd E. Barnhart
%A Viktoriya Bondarenko
%J Archive of "NPJ Parkinson's Disease".
%D 2018
%R 10.1038/s41531-018-0057-1
%X 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£¿¡À£¿SE) in the cardiac left ventricle in three select levels from base to apex and across regions. Treatment£¿¡Á£¿Region£¿¡Á£¿Level ANOVA analysis revealed a significant difference at 12 weeks after neurointoxication (F(35, 280)£¿=£¿2.10, p£¿<£¿0.034, ¦Çp2£¿=£¿0.21) and no significant difference at baseline (F(35, 280)£¿=£¿0.70, p£¿>£¿0.711, ¦Çp2£¿=£¿0.081) or 1 week (F(35, 280)£¿=£¿0.78, p£¿>£¿0.510, ¦Çp2£¿=£¿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£¿¡Á£¿Region (quadratic)£¿¡Á£¿Level (linear): 33.24%, p£¿>£¿0.084, ¦Çp2£¿=£¿0.327]. Simple interaction tests evaluating plot shape independently for each treatment confirmed distinct trends in the Region£¿¡Á£¿Level shape (pioglitazone, quadratic£¿¡Á£¿linear: 67.92%, p£¿<£¿0.019; placebo, cubic£¿¡Á£¿linear: 26.61%, p£¿<£¿0.004)
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045637/