Franck Debarbieu

23 mars 2012

IBDML, Marseille

Intravital imaging of cellular interactions at play in the pathological central in the nervous system

invité par Ivo Vanzetta

Central nervous system physiology relies on complex interactions between many different cells types including neural but also vascular and immune cell populations. Disregulation of the symbiotic interactions between these cells occurs in pathological conditions but its contribution to disease initiation and progression has been difficult to characterize. Tools were indeed so far lacking to study cellular interactions dynamically over weeks in a given subject. Our efforts have thus been focused on developing intravital imaging methodologies as well as mouse models of CNS pathologies to describe in time and space, at subcellular resolution, the role of selected cell populations in disease evolution. In vivo two-photon ( 2P) microscopy on multicolor fluorescent mice have highlighted an outstanding role of the vascular scaffold for axon regeneration after spinal cord injury as well as for brain infiltration by glioblastoma tumor cells. For both pathologies moreover, in vivo 2P showed that similar immune cell subtypes are sequentially recruited in the pathological CNS with typical distribution patterns. The functional relevance of immune cell interactions with regenerating axons or glioblastoma tumor cells is currently under investigation to understand the specificity of immune response that could be responsible for neuronal healing in spinal injury and for uncontroled cell proliferation to death in tumors 2P microscopy can however not access the immune response in the entire CNS nor the systemic consequences of the CNS pathology because of limited penetration of visible photons. To overcome this limitation we are currently collaborating on the development of spectral X-ray microCT to achieve multicolor imaging of several physiological components in the whole mouse body. This methodology should prove useful to evaluate the efficacy and specificity of drug treatments both in preclinics and clinics.