GABA_AR IgG- and Fab-induced increased mortality. (A–C) Immunofluorescence stainings on brain sections from C57BL/6 mice after cerebroventricular infusion (cv-inf.) of the indicated GABA_AR or control mAbs over 14 d. Detection with anti-human Fc-specific antibody (red) or anti-human Fab-specific antibody (green; insert in B) revealed characteristic hippocampal mAb deposition of #113-115 IgG (A) and #113-115 Fab (B). (C) Not seen in control animals receiving control IgG (#mGO53). Representative scale bars indicate 100 µm. (D) Kaplan-Meier plot for survival of C57BL/6 mice after cerebroventricular infusion over 14 d of indicated mAbs as IgG in high or low dose (1.5/0.3 µg IgG per hour) or as Fab in high dose. Survival was significantly different as analyzed using log-rank Mantel-Cox (P ≤ 0.0001), followed by ANOVA, post hoc Tukey's multiple comparisons (***, P ≤ 0.001; or not shown when P > 0.05; n = 5–7 animals per group). (E–H) Quantifications of the indicated total (E and F) and surface (G and H) proteins from murine brain homogenates after cerebroventricular mAb infusion as analyzed by Western blotting and normalized to mean of control IgG group. Each dot represents one hemisphere, n = 10 per condition. Bars indicate mean ± SEM.