Fig. 4

PARP inhibition prevents adhesion to and migration of monocytes across BMVEC monolayers preserving the barrier. Primary human monocytes were treated for 24 h with PARPi (AIQ, olaparib, EB47, talazoparib), calcein-labeled, washed, and then added to BMVEC monolayers (untreated or treated for 24 h with TNFα). Treatments were removed prior to the addition of monocytes. Adhesion to (a) and migration of (b) monocytes across blood-brain barrier models were measured and are presented as fold difference compared to TNFα-only control (mean ± SEM) for each treatment from at least quadruplicate determinations, which was assigned a value of 1 (7600 relative fluorescent units for adhesion or equivalent to 37 migrated cells). *P < 0.05, **P < 0.01 indicate significance vs. non-treated. TEER, an indicator of barrier integrity, was continuously measured in BMVEC monolayers treated with or without TNFα following the addition of primary human monocytes that had been treated with PARPi. c Dose-dependent treatment of monocytes with talazoparib at 10, 25, or 100 nM. d Treatment of monocytes with AIQ, olaparib, EB47 at 10 μM, and talazoparib at 100 nM; the percent change in TEER at 3, 10, and 17 h is shown. Data are presented as the percent change from baseline TEER (mean ± SEM) for at least six replicates (100 % equals a resistance of 644 Ω). ***P < 0.005 indicate significance vs. non-PARPi treated