Journal: CNS Neuroscience & Therapeutics

Article Title: KCC2 Dysfunction Mediated by Microglial BDNF / TrkB Signaling Exacerbates Early Post‐Stroke Seizure Susceptibility

doi: 10.1002/cns.70795

Figure Lengend Snippet: CLP290 inhibition of KCC2 expression downregulation reduces epilepsy susceptibility after MCAO‐R. (A, B) Western blot quantification of mKCC2 relative to GAPDH (A) and NeuN (B) in whole hippocampal tissue (Sham: N = 4, MCAO‐R: N = 7, MCAO‐ R + CLP290: N = 7). CLP290 attenuated the downregulation of mKCC2 in surviving neurons. (C, D) Proportions of mice at each seizure level in each group at the initial PTZ dose of 40 mg/kg (C) and cumulative 50 mg/kg PTZ (D). (E) Proportion of mice with seizure Racine IV‐V at 40, 50, 60, and 70 mg/kg cumulative dose of PTZ. CLP290 pretreatment significantly reduced the proportion of MCAO‐R mice with seizure Racine IV‐V at 40 mg/kg, 50 mg/kg, and 60 mg/kg PTZ doses. (F) Mean Racine seizure scores at cumulative PTZ doses of 40, 50, 60, and 70 mg/kg. CLP290 pretreatment significantly reduced the mean seizure scores in MCAO‐R mice. (G) Cumulative PTZ dose required to reach Racine IV–V seizures in each group. CLP290 pretreatment significantly increased the cumulative dose of PTZ associated with causing seizures to Racine IV‐V (Sham: N = 10, MCAO‐R: N = 13, MCAO‐ R + CLP290: N = 10). (H) Simplified schematic summarizing that CLP290, acting downstream on KCC2, restores KCC2 function after MCAO‐R, thereby normalizing E GABA , reducing neuronal hyperexcitability, and ultimately lowering seizure susceptibility. * p < 0.05, ** p < 0.01, and *** p < 0.001 compared to the Sham group; # p < 0.05 and ## p < 0.01 compared to the MCAO‐R group.

Article Snippet: FUR was purchased from Sigma‐Aldrich, and minocycline, K252a, and CLP290 were from MedChemExpress.

Techniques: Inhibition, Expressing, Western Blot