Administration of imipramine reduced microglial and astrocyte activation after hypoglycemia. To determine microglia and astrocyte activation, we conducted CD11b and GFAP staining, respectively. Hypoglycemia-induced microglia and astrocyte activation trigger an immune response. CA1 is vulnerable to injury by activated glial cells. (A) The green fluorescence (CD11b) shows activated microglia in the CA 1 region. Sham-operated groups displayed almost no microglial activation signal. However, after hypoglycemia, microglia cell intensity, number, and morphology were greatly boosted in the vehicle-treated group compared to the imipramine-treated group. (B) The grade of microglia activation in the CA1. (C) The red fluorescence (GFAP) shows activated astrocytes in the CA1 region. Sham-operated groups displayed almost no astrocyte activation, while the hypoglycemia-vehicle group showed significantly increased fluorescence intensity. (D) The bar graph represents the intensity of activated astrocytes in the CA1. However, after injury, imipramine prevented microglia and astrocyte activation in the CA1. Scale bar = 50 µm. Data are the mean ± SEM; n = 3 for each sham group; n = 9–10 for each hypoglycemia group. Individual data points (● = Sham-Veh, ■ = Sham-IMP, ▲ = HG-Veh, ▼ = HG-IMP). * Significantly different from the vehicle-treated group at p < 0.05.