09/02 – Franck DEBARBIEUX : Dynamic intravital 2P-CARS microscopy to explore the dual face of inflammation in the lesioned spinal cord

SPPIN’s webinar winter-spring 2021, 9 Feb at 10h30, online – Ask link to a SPPIN member.

Franck DEBARBIEUX, MCU , Team IMAPATH, Institut de Neurosciences de la Timone (UMR7289), Marseille, France

To characterize the cascade of inflammatory cellular events involved in neurodegenerative conditions, we have combined intravital Coherent Anti-stoke Raman Scattering microscopy with intravital two-photon fluorescence microscopy to image multicolor Thy1-CFP//LysM- EGFP//CD11c-EYFP transgenic reporter mice. Taking advantage of a unique technique of spinal glass window implantation, we can provide longitudinal description of cell dynamics in the same volume of interest over several weeks after a spinal cord lesion.

In a model of chemical lesion by LPC to induce selective intoxication of oligodendrocytes, we have shown that myelin damages were immediately followed by axon losses and further amplified by the recruitment of peripheral pro-inflammatory cells until day 4. From day 7 onward, regeneration started along with the recruitment of a second wave of anti- inflammatory immune cells whose density peaked after 2 weeks. Full recovery was observed within a month.

Such correlations between axonal densities and inflammatory cells subtypes were also observed with similar kinetics in a model of spinal cord trauma induced by a mechanical lesion. In this case moreover, anti-inflammatory cell recruitment could be accelerated by the insertion of biofunctionalized carbon microfibres inside the lesion. By helping regenerating axons to bridge the caudal and rostral ends of the lesion, these microfibres led to faster directed regrowth of axons. Altogether our data suggest that neuroprosthetic manipulation of the fate and phenotype of infiltrated monocytes derived cells represent an innovative strategy for neural tissue repair and spinal cord injury management.

Further reading

• El Waly B, Buttigieg E, Karakus C, Brustlein S, Debarbieux F. Longitudinal Intravital Microscopy Reveals Axon Degeneration Concomitant With Inflammatory Cell Infiltration in an LPC Model of Demyelination. Front Cell Neurosci. 2020; 14:165.
• El Waly B, Escarrat V, Perez-Sanchez J, Kaur J, Pelletier F, Collazos-Castro JE, Debarbieux F. Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury. Cells. 2021; 10(1):73.