The neurovascular Unit (NVU) consists of cerebral endothelial cells that interact physically and chemically with pericytes, astrocytes and microglial cells connected through the interactions with the basal lamina creating a functional barrier that regulates the movements of molecules into and out of the brain In the last two decades, the brain vasculature has increasingly been shown to have a key role in brain development, homeostasis, and disease. Recently the applicant has been identified a novel stem cell population with an exceptional neuronal differentiation potential in the perivascular space formed by extroflexions of meninges. The new cells named meningeal stem cells are activated by injury increasing their self renewal proliferation and migration properties and participate to the parenchymal reaction. In this project we will consider the perivascular meningeal stem cell activation in the context of the NVU interactions. We will challenge the hypothesis that the modulation of the meningeal stem cell activation can be done through the regulation of key metabolic factors and that this modulation can be exploit for the therapy of the neurological disorder. We will characterize and compare quiescent and injury-activated perivascular meningeal stem cells by using basic cell biology assay, trascriptomic and metabolic analysis. To specifically study meningeal stem cells interaction with the ECs and modulate their activation we will use RNA interference gene silencing, LV transduction and transgenic lines Moreover we will use spinal cord injury animal model and glioma animal model to test the therapeutic potential of meningeal stem cell activation. This multidisciplinary approach will shed light in how the meningeal stem cell interact with NVU and how their activation can be modulate as possible therapeutic target in the possible exploited of their activation can contribute to the neuro-angiogenesis in neurological disease.
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