Fractal analysis quantitates overt and subtle effects of naloxone and lipopolysaccharide on cultured rat microglia

Microglia are neuroimmune cells that respond to and affect events in the central nervous system in many species. Objectively monitoring and quantitating their response (activation) to pharmacological treatment is one challenge facing modern neuroscience. We applied methods based on fractal theory to analyze the morphology of cultured rat microglia exposed to activating and inhibiting stimuli. The box counting dimension (D_B) quantitated lipopolysaccharide's activating effects as an increase in the mean D_B and shift in its distribution and naloxone's inhibiting effects as a decrease in the mean D_B and shift in distribution. The D_B quantitated naloxone's obvious effects but also its visually undetectable effects on cells that do not appear to enter the activation sequence. In general, the results suggest that these discriminating capacities of the D_B may be a powerful tool for gauging microglial activation in areas such as incipient or ongoing responses associated with disease and drug use.