Functional and anatomical modifications of peritumoral tissue that occur along with glioma progression

Glioblastoma Multiforme (GBM) is the most aggressive form of brain tumors. It affects 3 in 100,000 people and has a median survival of 15 months. GBM is known to infiltrate the surrounding brain parenchyma, interacting with neuronal tissue. Specifically, tumoral cells induce neuron hyper-excitability while peritumoral cells seem to regulate tumor proliferation and progression. This project aims to investigate how the plastic rearrangement of cortical areas occurs in glioma-bearing animals. We took advantage of Thy1-ChR2 transgenic mice, injected with two syngeneic lines of murine glioma cells (i.e. GL261 and PDGF+ Trp53-/- cells) into the motor cortex. Mice were optogenetically stimulated in 120 points per session (covering the entire extent of forelimb motor representation) at 3 different time points: baseline (before glioma cells injection), 14 and 21 days after tumor implantation. Glioma-bearing mice showed a strong remapping of cortical motor areas, together with an increased threshold required for eliciting a forelimb movement in the peritumoral area. Immunohistochemical analyses revealed a downregulation of PNNs and of inhibitory markers in the peritumoral cortex. These findings demonstrate that the peritumoral tissue shows biochemical reorganization and transformation along with glioma progression. Increasing our knowledge about these changes will help to understand the mechanisms of gliomas progression, that might be targeted using new therapeutic approaches.