title: Homology analysis detects topological changes of Iba1 localization accompanied by microglial activation.
abstract: The state of microglial activation provides important information about the central nervous system. However, a reliable index of microglial activation in histological samples has yet to be established. Here, we show that microglial activation induces topological changes of Iba1 localization that can be detected by analysis based on homology theory. Analysis of homology was applied to images of Iba1-stained tissue sections, and the 0-dimentional Betti number (b0: the number of solid components) and the 1-dimentional Betti number (b1: the number of windows surrounded by solid components) were obtained. We defined b1/b0 as the Homology Value (HV), and investigated its validity as an index of microglial activation using cerebral ischemia model mice. Microglial activation was accompanied by changes to Iba1 localization and morphology of microglial processes. In single microglial cells, the change of Iba1 localization increased b1. Conversely, thickening or retraction of microglial processes decreased b0. Consequently, microglial activation increased the HV. The HV of a tissue area increased with proximity to the ischemic core and showed a high degree of concordance with the number of microglia expressing activation makers. Furthermore, the HV of human metastatic brain tumor tissue also increased with proximity to the tumor. These results suggest that our index, based on homology theory, can be used to correctly evaluate microglial activation in various tissue images.
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sawano
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tsuchihashi
authors.affiliation: Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Watanabe
authors.affiliation: Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: k-nakane@sahs.med.osaka-u.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakane
authors.affiliation: Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: inagaki@sahs.med.osaka-u.ac.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*
chemical_list: C112986:AIF1 protein, human; C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins
keywords: Iba1 localization; brain tumor; cerebral ischemia; homology; microglial activation; topology