Characterizing microglia activation: a spatial statistics approach to maximize information extraction

Abstract

Summary Microglia play an important role in the pathology of CNS disorders, however, there remains significant uncertainty about the neuroprotective/degenerative role of these cells due to a lack of techniques to adequately assess their complex behaviour in response to injury. This talk briefly describes a novel technique for microglia analysis, combining improved immunohistological image analysis with spatial statistical techniques (Ripley‐K function and Dixon's χ2‐test). Using this approach, a comprehensive set of morphological parameters describing microglia activation status was developed to characterise microgliosis in a murine optic nerve injury model. In addition to monitoring global changes in microglia density, nearest neighbour distance, and regularity index, cluster analyses based on changes in soma size and roundness were used to yield novel insights into the behaviour of different microglia phenotypes. These methods should be considered a generic tool to quantitatively assess microglia activation status, to profile these phenotypic changes into microglia subpopulations, and to map their spatial distributions in virtually every CNS region and disease state.

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

“…Compared to control mice, the average of soma size increased (56.85 vs. 68.32 μm 2 ) ( Figure 2D ). The result demonstrated the LPS exposure leads to activated microglia that features bigger soma size than ramified microglia called “resting” cells ( Kozlowski and Weimer, 2012 ; Davis et al, 2017 ). Taken together, these results demonstrate that LPS-induced neuroinflammation may activate microglia, leading to morphological alterations that suggest an activated state ( Liu and Hong, 2003 ).…”

Quantification of Huntington’s Disease Related Markers in the R6/2 Mouse Model

“…We found a general tendency of somewhat higher Iba1 immunoreactivity in R6/2 mice, which was significant in the hippocampus of 15 weeks old mice. There are several factors that may contribute to this difference, such as larger size of microglia, increased Iba1 expression, and a higher number of activated microglia ( Kozlowski and Weimer, 2012 ; Avignone et al, 2015 ; Davis et al, 2017 ). In fact, our panel of quantitative readouts generated during image analysis revealed that all these factors contribute to the differences in the percentage of immunoreactive area presented in Figure 6 .…”

Early alterations of neurovascular unit in the retina in mouse models of tauopathy

“…For cell counting, eight non-overlapping images were taken at the peripheral or middle region of each retinal flatmounts at 200 × magnification, then cells were manually counted and averaged for each sample. Microglial soma size and roundness and nearest neighbor distance (NND) were quantified using methods and formulas developed by Davis et al [15].…”