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Abstract :
[en] Traumatic brain injury (TBI) is currently one of the leading causes of global cognitive disorder and is mainly caused by falls, traffic accidents and sport contacts. During TBI, inertial forces cause shear stress in neurons and glial cells due to the deformation of brain tissues. Accumulative evidence suggests that neuroinflammation caused by mechanically activated glial cells plays an important role in the physio-pathological processes of TBI but this remains poorly understood.
To address this question, we first developed an inertia-driven model using organotypic hippocampal slice cultures (OHSC) providing near-in vivo cell interactions. Results showed a time-dependent diminution of synaptic connections due to the mechanical activation of microglia. Furthermore, our findings show that dendritic arborisation rapidly collapsed but progressively recovered over time alongside the microglial activation.
Then, we used cortical neuronal networks of controlled architectures [1] to decipher the role of mechanically-activated astrocytes on neuronal network connectivity. We show that the culture medium of activated astrocytes modulates significantly the neuronal expression of TNF-α receptors. Indeed, we observed a decrease of TNFR1 expression, while TNFR2 expression was increased after 5 days. Moreover, ELISA experiments showed a large increase in the concentration of TNF-α in harvested stretched astrocyte culture medium compared to control astrocyte culture. Altogether, our results decipher positive or negative modulation of neuronal connectivity by mechanically activated glial cells.
[1] J. Lantoine et al. Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures. Biomaterials 89, 14-24 (2016)