STATE OF THE ARTAcceuil 2020
Spinal cord injuries (SCI) that affect over 2.5 to 4 million patients worldwide (40’000 in France) yield major handicaps from partial sensory-motor deficits to complete tetraplegia. It has been established that adult neurons have the intrinsic capacity for re-growth after injury, though not spontaneously. Following SCI, a glial scar composed of microglia and astrocytes surrounds the lesion site constituting a barrier that plays both detrimental and beneficial roles on spontaneous axonal re-growth. In our recent studies, we isolated either astrocytes or microglia and analyzed their transcriptomic signature SCI (Noristani et al. Molecular Neurodegeneration, 2016 and Noristani et al., Frontiers in Molecular Neuroscience, 2017). This approach, the first transcriptomic analysis of glial cells after SCI, brought new insights on injury-induced glial response and plasticity. We showed that the astrocytic response is dependent on the time post-injury and the lesion severity, as opposed to the microglial response which depends only on the time post-injury. Interestingly, glial plasticity is induced by SCI in both cell populations. Whereas approximately 5% of injury-activated microglia show an overexpression of astrocytic markers, SCI induces a conversion of over 10% of perilesional mature astrocytes into neuronal lineage. This reflects an endogenous injury-induced process of converting astrocytes into neuronal lineage. We have identified candidate genes, and in particular fibroblast growth factor receptor 4 (Fgfr4) that may induce this endogenous astrocyte-to-neuron conversion.



We are to pursuing and extending our multimodal approach to decipher mechanisms that underlie the absence of spontaneous axonal regeneration following spinal cord injury. Our project is based on three complementary research approaches:

Line 1 - We modulate the glial response following SCI either through the modification of candidate genes that we have identified in astrocytes or via an oral treatment that transiently deplete microglia proliferation.
Line 2 - We further develop the use of diffusion magnetic resonance imaging as a translational tool in SCI to evaluate outcomes of therapeutic strategies. We also develop biophotonics studies to implement analysis at tissue and cellular level.
Line 3 - In parallel, we develop a long-term clinical project to better characterize the human spinal cord using bioimaging techniques.