Fig. 5: ALK5 inhibition induces Cldn5 expression and attenuates kainic acid-induced seizures and BBB leakiness.
From: Microvascular stabilization via blood-brain barrier regulation prevents seizure activity
a Increased Cldn5 expression 24 h post treatment with RepSox (100 μM) (**p = 0.0029). b Increased trans-endothelial electrical resistance (TEER) with increasing doses of RepSox. c Decreased flux of FITC-Dextran-40 (FD40) with increasing doses of RepSox. d Decreased flux of FD40 following exposure of endothelial cells to transforming growth factor-β1 (TGFβ) or vascular endothelial growth factor (VEGF) in combination with 100 µM RepSox. e RepSox significantly increased Cldn5 mRNA (*p = 0.0182) without changing (f) Ocln and (g) Tjp2 expression. h Experimental outline of RepSox treatment in the intrahippocampal kainic acid (KA) induced seizure model. i Reduced Racine score in RepSox treated mice (**p = 0.0039) compared to saline (Sal). j Decreased cFos expression in the cortex (**p = 0.0036) and hippocampus (*p = 0.0461) post treatment with 10 mg/kg RepSox. Scale bar, 100 μm. k Decreased IgG (green) extravasation in the cortex (*p = 0.0243) and hippocampus (**p = 0.0038) post treatment with 10 mg/kg RepSox. Scale bar, 100 μm. Data represent means ± s.e.m.; number of independent experiments or animals (n) is indicated on graphs. Two-way ANOVA followed by Bonferroni’s multiple comparison test for tight junction qPCRs; one-way ANOVA followed by Tukey’s multiple comparison test for cell culture experiments; two-sided unpaired t-test for in vivo studies. *p < 0.05; **p < 0.01; ****p < 0.0001. Source data are provided as a Source Data file.
