The role of cell density in the survival of cultured cerebellar granule neurons

The dependence for survival of cerebellar granule neurons on the cell densi ty was examined both experimentally and theoretically. The results of batch experiments revealed that the cell survival index (CSI) was inappreciable, if-cell density was below a critical level. If cell density exceeded this critical value, CSI increased with the increase in cell-density. In additio n, CSI was significantly increased by using a conditioned medium from the d ense cultures. This suggests that not only cell density promotes survival o f neurons, but-also an increased concentration of growth factors produced b y neurons has a direct effect on the survival of the neurons. A quantitativ e model describing the distribution of the growth factor at different cell densities was pro-posed to investigate the role of cell density in the surv ival of the neurons. We showed the existence of a critical level for cell d ensity, and good agreement in the improvement of CSI was found between the theoretical prediction and the experimental result. Finally, the average co ncentration of growth factor necessary for cell survival based on our model was in a reasonable range compared to the practice of the addition of neur otrophic factors to the medium of cultured cerebellar granule neurons. (C) 2000 John Wiley & Sons, Tnc.