Fig 2: Lithium protected the BBB in adult mice with ICH. (A) Representative images of the brain showing EB leakage in control mice with ICH and reduced leakage in mice treated with LiCl at a dose of 3.0 mmol/kg. (B) Quantitation of EB fluorescence. n = 5 mice per group. (C) Quantification of relative IgG signal densities. n = 5 mice per group. (D) Immunofluorescence staining of endogenous plasma IgG (green) leakage from vessels (red) after ICH in mice treated with or without LiCl. (E) Schematic illustration showing where the images in (D) were taken from. Perihematomal regions (indicated by black squares) were selected and imaged. Scale bar, 100 µm. *p < 0.05, **p < 0.01. ICH, intracerebral hemorrhage; BBB, blood–brain barrier

Fig 3: Lithium upregulated Wnt/ß-catenin signaling in the brain endothelium after ICH in vivo. (A) Coimmunofluorescence staining for active ß-catenin (green) and CD31 (red) around the hematoma areas. Scale bar, 100 µm. (B) The active ß-catenin signal density was normalized to the CD31 signal area. n = 3 mice per group. **p < 0.01. ICH, intracerebral hemorrhage

Fig 4: Lithium protected the BBB by regulating endothelial tight junctions following ICH. (A) Levels of tight junction protein markers (ZO-1, occludin and claudin-5) and basement membrane proteins in ICH mice as measured by Western blotting. (B) Quantitation of the bands in (A). n = 3 mice per group. The experiments were repeated twice, and representative results are shown. (C) Coimmunofluorescence staining for claudin-5 or ZO-1 (green) and CD31 (red) around the hematoma areas. Scale bar, 100 µm. (D) The positive signal density was normalized to the CD31 signal area. n = 5 mice per group. Scale bar, 100 µm. *p < 0.05, **p < 0.01. ICH, intracerebral hemorrhage

Fig 5: Lithium improved stroke outcomes in adult mice with ICH. (A) Experimental procedure. (B) Hematoma volumes in mice with ICH after 3 mmol/kg LiCl or vehicle treatment. (C) Quantification of the hematoma volumes in mice. n = 6 mice per group. (D) Brain water content in the contralateral hemisphere (Contra) and ipsilateral hemisphere (Ipsi). n = 5 mice per group. (E) The neurologic deficit scores as well as the grab test and horizontal ladder test performances of mice with ICH treated with LiCl or vehicle. n = 6 mice per group. *p < 0.05. ICH, intracerebral hemorrhage; Contra, contralateral hemisphere; Ipsi, ipsilateral hemisphere