LBT-3627 pretreatment is neuroprotective in vivo. A, Photomicrographs of TH+Nissl+ neurons in the SN and TH+ striatal termini (STR) in mice treated with PBS, MPTP, or pretreated with VIP, LBT-3393, or LBT-3627 before MPTP intoxication (40× image; scale bar, 200 μm). Sections were immunostained with anti-TH and HRP-conjugated secondary antibody and visualized with DAB. SN sections were counterstained with thionin. B, Total numbers of surviving dopaminergic neurons (TH+Nissl+) and nondopaminergic neurons (TH−Nissl+) in the SN after MPTP treatment alone or pretreatment with VIP, LBT-3393, or LBT-3627. Percentages of spared dopaminergic neurons are included for each treatment (10× image; scale bar, 1000 μm). D, Total number of TH+Nissl+ and TH−Nissl+ neurons within the SN after MPTP intoxication alone or with pretreatment of [D-p-Cl-Phe6,Leu17]-VIP (Antag), scrambled peptide (LBT-SCR), or coadministration of VIP, LBT-3393, or LBT-3627 with antagonist. F, Dose–response for LBT-3627 at varying pretreatment doses of 1.5, 5, 15, 45, and 90 μg/dose followed by MPTP intoxication. G, Linear regression analysis of dose–response, R2 = 0.4614 p = 0.001. C, E, Relative TH densitometry of striatal dopaminergic termini after pretreatment. B–F, Differences in means (±SEM, n = 8) were determined where p < 0.05 compared with groups treated with PBS (a), MPTP (b), VIP (c), or LBT-3393 (d).