Differentiating Grades of Microglial Activation with Fractal Analysis

Microglia affect and are sensitive to events in the central nervous system , changing in morphology and function as they respond to and resolve disruptions. Monitoring microglia is, therefore, an important goal of neuroscience. We investigated morphological changes in cultured mouse microglia, using the box counting fractal dimension (DB), lacunarity (Λ), and other measures. The DB and Λ corresponded well to visually applied classification systems of these cells. Complementing such systems, which depend on grossly visible differences between cells, the DB also differentiated between visually indistinguishable microglia in different functional states (i.e., deramifying versus reramifying). The results suggest that fractal analysis may help determine if a microglial cell is “resting”, rousing itself for action, acting subtly, or returning to a resting state. Because of the awesome potential microglia have to affect events in the central nervous system, the implications of this for the study of human health and disease are profound.

[1]  Noth,et al.  Dynamics of microglial activation in the spinal cord after cerebral infarction are revealed by expression of MHC class II antigen , 1998, Neuropathology and applied neurobiology.

[2]  K. Dobrenis.  Microglia in cell culture and in transplantation therapy for central nervous system disease. , 1998, Methods.

[3]  G. Kreutzberg.  Microglia: a sensor for pathological events in the CNS , 1996, Trends in Neurosciences.

[4]  I. Everall,et al.  Motility and ramification of human fetal microglia in culture: an investigation using time-lapse video microscopy and image analysis. , 2002, Experimental cell research.

[5]  M. Dailey,et al.  Dynamics of microglial activation: A confocal time‐lapse analysis in hippocampal slices , 2001, Glia.

[6]  Marion E. Smith,et al.  Phagocytic properties of microglia in vitro: Implications for a role in multiple sclerosis and EAE , 2001, Microscopy research and technique.

[7]  W. B. Marks,et al.  A fractal analysis of cultured rat optic nerve glial growth and differentiation , 1991, Neuroscience.

[8]  R. Pawlinski,et al.  Morphology of reactive microglia in the injured cerebral cortex. Fractal analysis and complementary quantitative methods , 2001, Journal of neuroscience research.

[9]  W. B. Marks,et al.  Fractal methods and results in cellular morphology — dimensions, lacunarity and multifractals , 1996, Journal of Neuroscience Methods.

[10]  P. Mcgeer,et al.  Inflammation of the brain in Alzheimer's disease: implications for therapy , 1999, Journal of leukocyte biology.

[11]  J. Ellison,et al.  Matrix Remodeling after Stroke: De Novo Expression of Matrix Proteins and Integrin Receptors , 1999, Annals of the New York Academy of Sciences.

[12]  H F Jelinek,et al.  Use of fractal theory in neuroscience: methods, advantages, and potential problems. , 2001, Methods.

[13]  G. Raivich,et al.  In vitro model of microglial deramification: Ramified microglia transform into amoeboid phagocytes following addition of brain cell membranes to microglia‐astrocyte cocultures , 2001, Journal of neuroscience research.