(A) Box plots of Gene Ontology biological processes showing neuron-related transcriptional correlations for BrM cell lines relative to isogenic parentals (FC > 0.5 with P < 0.05). (B and C) Transcript levels of AMPA (B) and GABA-A (C) receptor components in primary breast cancer and B2BM samples (GSE184869) (n = 90); statistical analysis by Wilcoxon matched-pairs test. (D) Normalized photon flux from BLI images of control, flumazenil-, and levetiracetam-treated murine cohorts at the indicated time points after MDA-MB-231-BrM intracardiac injection; statistical analysis by multiple Mann-Whitney U test normalized to MDA-MB-231-Br3 control group at week 4. (E) Kaplan-Meier survival analysis for control and drug-treated murine cohorts following MDA-MB-231-BrM intracardiac injection until day 35 (vehicle [n = 15], flumazenil [n = 10], and levetiracetam [n = 10]). Statistical analysis by log rank (Mantel-Cox) test. (F and G) (Left) Representative H&E and corresponding GluR2 (F) or GABA(A)Rγ-II (G) IHC staining of NSG murine brain sections harboring MDA-231-BrM BMs. Scale bars: 500 μm (low power) and 100 μm (high power). (Right) Quantified GluR2 (F) or GABA(A)Rγ-II (G) IHC intensity in metastatic region (MR), white matter (WM), and gray matter (GM) regions [GluR2, n = 10; GABA(A)Rγ-II, n = 9]. Statistical analysis by 1-way ANOVA. (H and I) Representative IHC staining and intensity quantification for GluR2 (n = 7) (H) and GABA(A)Rγ-II (n = 7) (I) in human triple-negative B2BM tissue samples, assessing negative regions (NR), uninvolved healthy brain regions (HBR), and MR. Scale bars: 50 μm. Statistical analysis by 1-way ANOVA. Data are shown as mean ± SEM.