Resibufagenin

Thus, in an animal model of the pregnancy-dependent hypertensive syndrome, preeclampsia (PE), MBG was elevated before the advent of the hypertension and proteinuria. 33, 34 In addition, the antagonist of MBG, resibufagenin (RBG), corrected the hypertension in the rat model of PE and prevented hypertension, proteinuria, and intrauterine growth restriction if given early in pregnancy to animals destined to develop this syndrome. 35 – 37 Furthermore, in a small series of PE patients ( n = 19), MBG was elevated in 85% of the samples compared to those obtained in normal pregnant patients ( n = 34). 38 In rats in which traumatic brain injury had been induced, urinary MBG was elevated above that obtained in sham animals and was reduced to sham levels in rats treated with RBG 24 hours after the imposition of a brain contusion. 39 Furthermore, on histologic examination of the brain, RBG reduced gliosis and vascular injury and prevented scar formation. 39 In in vitro studies, MBG caused hyperpermeability of human brain endothelial cell monolayers 9 by altering apoptotic signaling. 13 MBG causes oxidative stress, 40 which is prevented, in the rat PE model, by RBG administration. 41 Finally, in preliminary experiments, MBG was elevated in patients with acute respiratory distress syndrome 42 and caused vascular leak in rat lung endothelial cell monolayers. 13 Based upon the observations previously obtained in both in vivo and in vitro studies and those described above in concussed athletes, we believe that MBG is an excellent candidate to evaluate the presence and status of the inflammation associated with the brain pathology observed in TBI.