As the first and main form of active immune defense in the central nervous system, microglial cells usually exhibit complicated intracellular calcium (Ca2+) activity that can regulate the downstream components of signaling cascades. In the present work, spontaneous oscillations of the cytosolic calcium concentration ([Ca2+](c)) in multi-BV-2 microglial cells were observed by video microscopy. These cells exhibited random spikes of Ca2+ oscillations. Cross-correlation analysis of the temporal dependence of the oscillations indicated the existence of cell-cell communication mediated by extracellular messengers. Numerical simulations based on a simple mathematical model suggested that these communications could induce random spikes of spontaneous Ca2+ oscillations in the multi-cell system. Short-time imaging analysis of random spikes in different regions of a single cell showed that spontaneous Ca2+ oscillations resulted from Ca2+ wave generated by other cells as well as from calcium elevation inside the cell. Taken together, our data demonstrate that cell-cell communication existed between the BV-2 microglial cells in vitro and further resulted in the random spikes of spontaneous Ca2+ oscillations. (C) 2013 Elsevier Inc. All rights reserved.