Fig. 2: The temporal relationship between microglia-vessel migration and BBB permeability during systemic inflammation.

a Image series from a single mouse demonstrate the time course of microglia migration to cerebral vessels during the development of systemic inflammation induced by daily LPS injections. b Effects of daily LPS injections on the proportion of microglia in contact with cerebral vessels. Graphs show data from control (without LPS) and LPS (with LPS) experiments. Blue shadow indicates LPS injections (i.p.). c Effects of LPS on the total number of microglia in each image field on each day. LPS had no significant effect on total microglial density. d A series of typical images from a single mouse demonstrates the time course of changes in BBB permeability after systemic LPS injection. e Effects of daily LPS injections or control on dextran leakage from blood vessels. The relative leakage of 10 kDa dextran was significantly increased from 4 to 7 days after LPS injection. f Quantification of the size selectivity of BBB permeability after systemic LPS injection using different molecular size dextrans. g Typical images (left panels) and mean data (right panel) show the effects of partial microglia ablation (Dox-Off) on the density of microglia in the brain parenchyma and associated with vessels. The density of vessel-associated microglia was significantly decreased in Dox-Off mice as compared with Dox-On mice. h A series of typical images from a single Dox-On (upper panels) and Dox-Off (lower panels) mouse illustrate the effects of microglia ablation on BBB permeability during systemic inflammation induced by daily LPS injection. Time course of BBB permeability changes during LPS injections Dox-Off and Dox-On mice. Microglia ablation induced a significant increase in BBB permeability during the early phase of systemic inflammation (Day 3) and a significant reduction in the later phase. In all line graphs, light lines indicate data from an individual animal (b, c, e, f, h), while the dark lines and error bars show mean ± SD. NS not significant. *P < 0.05, **P < 0.01 and *** P < 0.001. Scale bars in all panels: 50 μm.