Fig. 4: Protective effect of VK on the blood–brain barrier (BBB) in stroke mice.

a Experimental design: in addition to the sham group, mice (8–10 weeks, male) were subjected to MCAO for 60 min. Mice were randomized into four groups: sham group, vehicle group, and VK (150 and 300 µg/kg) groups. Mice were administered VK at 0, 4, 22.5, and 46.5 h after MCAO/R and BBB integrity was assessed by Evans blue (EB) and transmission electron microscope (TEM). b Brain samples were stained with EB. c EB content in damaged (right) hemisphere was quantized. d Schematic of BBB. The BBB mainly consists of endothelial cells (EC), pericytes (PC), astrocytes (Ast), neurons, tight junctions (TJs), and the basement membranes (BM). The main components of the BBB are cerebral microvascular ECs joined by TJs, thus restricting exogenous molecules into the brain. e The structure of the BBB was observed by TEM. In the sham group (e1–3), the capillary morphology was regular, the EC and TJ were complete, the thickness of the BM was uniform and continuous around the outside of EC, and the structure of mitochondria (Mt) was clear. When the BBB was destroyed (e4–6), the BM and TJ were largely dissolved and shed, and the Ast showed extreme edema; there were large electronic blank areas and the Mt was loose or vacuolar, which were relieved by VK treatment (e7–12). The marks with different symbols indicate the constituent cells or matrix of the BBB. Scale bars: 2 µm. Data are expressed as the mean ± SD, n = 5. Values were analyzed using one-way analysis of variance (ANOVA) with the Tukey multiple comparisons test.