9 | Perivascular macrophages in ischaemic endothelial function

Regulation of endothelial functions by macrophages may be mediated by humoral factors, such as those of the complement pathway, which is activated by tissue damage and modulates ischaemic and traumatic brain injury. This project will test the hypothesis that the complement factors modulate the ability of perivascular macrophages to regulate endothelial permeability and blood-brain barrier (BBB) function. We will assess how phenotypic and polarisation markers of perivascular macrophages are changed by ischaemia and how these changes impact on BBB functions in relation to complement activation. This project will use in vivo and in vitro models of ischaemia and different tools, including transgenic mouse lines, in vivo two-photon microscopy, quantitative immunofluorescence, superresolution microscopy and single-cell RNA-seq.

Publications

  • Fumagalli S, Fiordaliso F, Perego C, Corbelli A, Mariani A, De Paola M, De Simoni MG. The phagocytic state of brain myeloid cells after ischemia revealed by superresolution structured illumination microscopy. J Neuroinflammation 2019 ; 16 : 9
  • Orsini F, Fumagalli S, Császár E, Tóth K, De Blasio D, Zangari R, Lénárt N, Dénes Á, De Simoni MG. Mannose-Binding Lectin Drives Platelet Inflammatory Phenotype and Vascular Damage After Cerebral Ischemia in Mice via IL (Interleukin)-1α. Arterioscler Thromb Vasc Biol. 2018 Nov; 38(11):2678-2690.
  • Fumagalli S, De Simoni MG. Lectin complement pathway and its bloody interactions in brain ischemia. Stroke 2016;47:3067-3073.
  • Perego C, Fumagalli S, Zanier E R, Carlino E, Panini N, Erba E, De Simoni MG. Macrophages are essential for maintaining a M2 protective response early after ischemic brain injury. Neurobiol Dis 2016;96:284-293.
  • Orsini F, Villa P, Parrella S, Zangari R, Zanier ER, Gesuete R, Stravalaci M, Fumagalli S, Ottria R, Reina JJ, Paladini A, Micotti E, Ribeiro-Viana R, Rojo J, Pavlov VI, Stahl GL, Bernardi A, Gobbi M, De Simoni MG. Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia. Circulation 2012; 126:1484-1494.


Potential secondments

MIM (Paul Vulto), month 16-18; UNIBERN (Britta Engelhardt), month 22-24; UKLFR (Marco Prinz), month 33-35

Host Organisation:
Laboratory of Inflammation and Nervous System Diseases, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
Supervisor:
Maria-Grazia De Simoni, Stefano Fumagalli