Fig. 4: Inducible Cldn5 knockdown mice develop spontaneous seizures and neuroinflammation.

a Schematic outline of inducible knockdown mouse model. b Cldn5 significantly suppressed following 4 weeks of doxycycline (Dox) treatment (**p = 0.001). c Percentage of mice with spontaneous recurrent seizures (SRS) following 4 weeks of Dox treatment (****p < 0.0001). d Representative EEG traces following 4 weeks of Dox treatment. e IBA1 (green) quantification post claudin-5 suppression with decreased cellular endpoints (**p = 0.0088), and increased IBA1 positive cells (***p = 0.0005). Scale bar, 50 µm. f, g Experimental outline for recovery experiment. Increased GFAP levels in the dentate gyrus (DG ****p < 0.0001), CA1 (***p = 0.0001) and CA3 (***p = 0.0007) of mice following 4 weeks of doxycycline treatment are reversed following doxycycline withdrawal in the DG (***p = 0.0002 vs Cre positive 4 weeks). Scale bar, 100 µm. Increased seizure behaviour as scored according to Racine scale (****p < 0.0001 for Cre− vs Cre+ (Dox)) decreased following Dox removal (***p = 0.0004 for Cre+ (Dox) vs Cre+ (off Dox). Data represent means ± s.e.m.; each datapoint represents one animal. Number of animals (n) is indicated on graphs. Mantel–Cox test for SRS analysis; two-sided unpaired t-test for qPCR and microglia morphology; two-way ANOVA followed by Bonferroni’s multiple comparison test for reversibility study. **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.