Vittoria Berutto Arianna Rizzo

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Vittoria Berutto Arianna Rizzo CMB Master Degree Neurobiological track 2018/2019 Vittoria Berutto Arianna Rizzo

Introduction: What are microglia? Neurovascular concept Regulation of microglial switch

Scientific questions: May astrocytes and endothelium cells contribute to a gliovascular switch for microglial activation? Are these differentially activated microglia toxic or beneficial towards neurons?

What kind of cell types are studied? Microglia Astrocytes Cerebral endothelial cells

Different effects of oxygen-glucose-deprived endothelium versus astrocytes on microglial activation Microglial morphology Quantification of cytokines and growth factors

d C Expression levels of CD11b, CD45, CD86 and MHC II Expression levels of NOS2, CD86, CD206 and Arg1

Alteration of microglial functions after treatment with conditioned media from endothelial cells or astrocytes

Different effects of endothelial-activated versus astrocytes-activated microglia on neurons Neuronal cell viability Representative hippocampal neurons transfected with pEGF-C1 vector

Discussion and Conclusions: Endo-CM-treated microglia: release of large amounts of TNFα and IL- 1β upregulation of CD45, CD86, MHCII and NOS expression Inhibition of microglial migration and phagocytosis Astro-CM-treated microglia: Increase in the production of IGF-1 upregulation of CD206 expression Enhancement of phagocytosis

neuronal consequences: Different states of microglial activation neuronal consequences: Endothelial-activated microglia are neurotoxic Astrocytes-activated microglia promote neuroplasticity HYPOTHESIS OF A GLIOVASCULAR MECHANISM FOR REGULATING THE MICROGLIAL SWITCH

a model for in vivo studies Microglial switch: a model for in vivo studies

Future perspectives: To understand how microglia become activated and how they mediate neuroinflammation Beneficial and detrimental effects of microglial functions in brain ischemia and trauma Modulation of microglial behaviors is clearly an important topic of investigation Huge potential for the development of new therapeutic strategies in acute brain injury

Bibliography: Xing, C., Li, W., Deng, W., Ning, M., & Lo, E. H. (2018). A potential gliovascular mechanism for microglial activation: differential phenotypic switching of microglia by endothelium versus astrocytes. Journal of neuroinflammation, 15(1), 143. Kim, J. Y., Kim, N., & Yenari, M. A. (2015). Mechanisms and potential therapeutic applications of microglial activation after brain injury. CNS neuroscience & therapeutics, 21(4), 309-319. Loane, D. J., & Byrnes, K. R. (2010). Role of microglia in neurotrauma. Neurotherapeutics, 7(4), 366-377.