Fig. 2

RBC-EVs cross the BBB after 3 injections of LPS: Clearance of intravenously injected ¹²⁵I-EVs from blood. Pharmacokinetic parameters were calculated for the relation between log10 (%Inj/mL) and time a For ¹²⁵I-EVs, calculations based on the slope yielded a half-time clearance of 44 min and based on the Y-intercept, yielded an initial volume of distribution (Vd) of 6.02 mL. For Tc⁹⁹m-albumin, half-time clearance was 61 min and an initial Vd was 1.32 mL. Uptake of ¹²⁵I-EVs and Tc⁹⁹m-Alb by brain b Unidirectional influx rates (μL/g-min) for brain were calculated by multiple-time regression analysis, n = 15/group. Unidirectional influx rates of ¹²⁵I-EVs and Tc⁹⁹m-Alb by brain following LPS c Multiple-time regression analysis was used to calculate the unidirectional influx rates of delta values (brain serum ratios for ¹²⁵I-EVs with brain/serum ratios for Tc^99m-Alb subtracted) vs exposure time. LPS significantly increased the uptake by brain of ¹²⁵I-EVs (p < 0.05), n = 15/group. Capillary depletion with or without LPS d The majority of RBC-EVs was in the parenchymal space. LPS significantly increased the crossing of ¹³¹I-EVs in brain parenchyma. Values are means ± S.E.M. Student's t-test *** p < 0.001, n = 7-8/group. LPS dose-dependently decrease TEER (e) and increase the permeability of ¹²⁵I-EVs f Results are expressed as % of vehicle (74.6 ± 11.9 Ω cm² (e); 2.7 ± 0.4 × 10⁻⁵ cm/min (f)). Values are means ± S.E.M. Kruskal-Wallis test ** p < 0.01, *** p < 0.001 vs vehicle, n = 8–9