PMC:7463108 / 55482-59484 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T779 0-342 Sentence denotes Using a primary human brain microvascular endothelial cell (BMEC) and astrocyte co-culture model, Mahajan et al. (2008) were among the first to demonstrate that co-exposure to morphine and HIV-1 Tat resulted in greater increases in TNF-α and IL-8 levels and decreases in barrier tightness (measured by TEER) than either morphine or Tat alone.
T780 343-583 Sentence denotes Morphine and Tat co-exposure also additively increased JAM-2, while zonula occludens-1 (ZO-1) levels were decreased by morphine or by Tat individually, and occludin protein levels were decreased by morphine alone but not Tat (Mahajan et al.
T781 584-590 Sentence denotes 2008).
T782 591-752 Sentence denotes Using the inducible Tat transgenic mouse model, Leibrand et al. (2019), also demonstrated that HIV-1 Tat and morphine act independently to disrupt BBB integrity.
T783 753-926 Sentence denotes In these studies, morphine, and to a lesser extent Tat, exposure increased the leakage of fluorescently labeled dextrans from the circulation into the brain (Leibrand et al.
T784 927-948 Sentence denotes 2017, 2019) (Fig. 3).
T785 949-1066 Sentence denotes Morphine exposure decreased the penetration of select ARVs in the brain, in a region-specific manner (Leibrand et al.
T786 1067-1082 Sentence denotes 2019) (Fig. 3).
T787 1083-1286 Sentence denotes Morphine exposure also resulted in increased expression and function of the drug efflux transport protein, P-gp, suggesting a mechanism by which morphine decreased the ARV concentrations (Leibrand et al.
T788 1287-1293 Sentence denotes 2019).
T789 1294-1440 Sentence denotes This finding suggests that morphine exposure could impact the efficient delivery of any therapeutic drug that is a substrate of P-gp into the CNS.
T790 1441-1572 Sentence denotes Future research should also investigate morphine’s impact on other drug transport proteins important for ARV delivery to the brain.
T791 1573-1674 Sentence denotes Fig. 3 Effects of HIV-1 Tat and morphine on BBB leakiness and on antiretroviral brain concentrations.
T792 1675-1965 Sentence denotes After 14 days of Tat induction, there was a significant increase in the 10 kDa (Cascade Blue®) tracer leakage into the brain in Tat + placebo as compared to Tat − placebo mice (*p < 0.05) and in Tat − mouse brains upon exposure to morphine as compared to Tat − placebo mice (*p < 0.05) (a).
T793 1966-2314 Sentence denotes There was a significant main effect of morphine, resulting in reduced integrity of the BBB and increased leakage of the higher molecular weight (40 kDa and 70 kDa) tracers in morphine-exposed groups as compared to the those groups (Tat + and Tat − together) not exposed to morphine (placebo) (#p < 0.05; significant main effect of morphine) (b, c).
T794 2315-2474 Sentence denotes Data represent the fold change in mean fluorescence intensity ± SEM; n = 8 Tat−/placebo, n = 6 Tat+/placebo, n = 9 Tat−/morphine, and n = 7 Tat+/morphine mice.
T795 2475-2650 Sentence denotes Additionally, morphine exposure increased horseradish peroxidase (HRP) extravasation from the vasculature into the perivascular space and/or parenchyma in the striatum (d, e).
T796 2651-2888 Sentence denotes HRP antigenicity was detected by indirect immunofluorescence (red) in tissue sections counterstained with Hoechst 33342 (blue) to reveal cell nuclei and visualized by differential interference contrast (DIC)-enhanced confocal microscopy.
T797 2889-3050 Sentence denotes HRP extravasation into the striatal perivascular space/parenchyma was especially prevalent in morphine-exposed mice (arrowheads; left-hand panels in e versus d).
T798 3051-3321 Sentence denotes The dotted lines (············) indicate the approximate edge of the capillaries/post-capillary venules; while intermittent dotted lines (· · · · · · ·) indicate the approximate edge of a partly sectioned blood vessel that appears partially outside the plane of section.
T799 3322-3389 Sentence denotes The asterisks (*) indicate white matter tracts within the striatum.
T800 3390-3441 Sentence denotes Representative samples from ≥ n = 4 mice per group.
T801 3442-3480 Sentence denotes All images are the same magnification.
T802 3481-3499 Sentence denotes Scale bar = 10 μm.
T803 3500-3557 Sentence denotes Antiretroviral tissue-to-plasma ratios in striatum (f–g).
T804 3558-3776 Sentence denotes Irrespective of Tat exposure, morphine significantly reduced the levels of dolutegravir (f) and abacavir (g), but not lamivudine (h), within the striatum, as compared to placebo. (* p < 0.05; main effect for morphine).
T805 3777-4002 Sentence denotes Data represent the tissue-to-plasma ratios ± SEM sampled from n = 9 Tat−/placebo, n = 9 Tat+/placebo, n = 6 Tat−/morphine, and n = 8 Tat+/morphine mice. (a–h) Modified and reprinted with permission from Leibrand et al. (2019)