Role of resident microglia in lymphoid neogenesis after rodent cerebral ischemia

Identifier:  TFG:2127

Handle: https://hdl.handle.net/20.500.11797/TFG2127

Authors:  Peiró Moreno, Carla

Abstract:
In certain inflammatory responses, it has been observed that lymphocytic infiltrates cluster in organized assemblies that can remain in the tissue for a long time. There is emerging evidence that these lymphoid follicles contribute to the maintenance of chronic inflammation through a sustained autoimmune response over time. Lymphoid neogenesis, the process of formation of these compartmentalized aggregates, is thought to be driven by lymphoid chemokines. However, the cell types involved after an acute cerebral ischemia remains unknown, which made us hypothesize about the role or resident microglia. Cx3cr1.FiDTR was used to deplete microglia at day 11 post-stroke. Mice underwent a middle cerebral artery occlusion during 60 minutes and samples were extracted 14 days after the surgery. Cx3cr1.FiDTR was found to be a consistent mouse model to study microglia functions after stroke. Nonetheless, a longer extent of the depletion would enable better research on long-term effects of this cellular subset. Immunohistological and expression analyses showed that depletion of resident microglia leads to an inhibition of lymphocytic accumulation in the brain 14 days after stroke. Cx3cr1.FiDTR mice also presented an altered cytokine expression profile after stroke, when compared to our previous data obtained in wild-type and 2D2 mice. We observed lower mRNA levels of the lymphoid chemokines Cxcl13, Cxcl12, and Ccl19. Ltβ and Cxcr5 genes presented a not significant tendency towards a decreased expression. Regarding to other myeloid populations, microglia depletion did not appear to change the recruitment of infiltrating monocytes and monocyte-derived macrophages. Therefore, it can be concluded that resident microglia is essentially needed in lymphoid neogenesis and its actively involved in the molecular changes triggered after cerebral ischemia in mice. Keywords: lymphoid follicles, lymphoid neogenesis, ischemia, microglia, Cx3cr1