title: Proliferation of parenchymal microglia is the main source of microgliosis after ischaemic stroke.
abstract: Stroke induces rapid activation and expansion of microglia, but the main source of microgliosis is controversial. Here we investigated the formation of microgliosis and infiltration of circulating cells in a photothrombosis stroke model by taking advantage of parabiosis and two-photon microscopy. We found that a small population of blood-derived CX3CR1(GFP/+) cells infiltrated the cerebral parenchyma, but these cells did not proliferate and were phenotypically distinguishable from resident microglia. CX3CR1(GFP/+) infiltrating cells also displayed different kinetics from reactive microglia. The number of CX3CR1(GFP/+) infiltrating cells peaked on Day 5 after stroke and then decreased. The decline of these infiltrating cells was associated with an active apoptotic process. In contrast, reactive microglia were recruited to the ischaemic area continuously during the first week after stroke induction. Immunohistology and in vivo two-photon imaging revealed that cells involved in the process of microgliosis were mainly derived from proliferating resident microglia. Expansion of microglia exhibited a consistent pattern and our in vivo data demonstrated for the first time that microglia underwent active division in regions surrounding the ischaemic core. Together, these results indicated that CX3CR1(GFP/+) infiltrating cells and reactive microglia represented two distinct populations of cells with different functions and therapeutic potentials for the treatment of stroke.
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 73000, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Shengru
authors.initials: S
authors.lastname: Pang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D003238:Connective Tissue / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000473:pathology*; D010775:Photic Stimulation; D054390:Receptors, CCR2 / Q000378:metabolism; D019707:Receptors, Chemokine; D020521:Stroke / Q000473:pathology*; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; D008840:Microfilament Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D049452:Green Fluorescent Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: infiltrating cells; microglia; microgliosis; parabiosis; stroke