Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

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Author
Pluchino, Stefano
Muzio, Luca
Alfaro-Cervello, Clara
Salani, Giuliana
Porcheri, Cristina
Brambilla, Elena
Cavasinni, Francesca
Bergamaschi, Andrea
Garcia-Verdugo, Jose Manuel
Comi, Giancarlo
Martino, Gianvito
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1093/brain/awn198Metadata
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Pluchino, Stefano, Luca Muzio, Jaime Imitola, Michela Deleidi, Clara Alfaro-Cervello, Giuliana Salani, Cristina Porcheri, et al. 2008. Persistent inflammation alters the function of the endogenous brain stem cell compartment. Brain 131, no. 10: 2564-2578.Abstract
Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation of non-migratory neuroblasts within the SVZ germinal niche. In parallel, we demonstrate a quantitative reduction of the putative brain stem cells proliferation in the SVZ during persistent brain inflammation, which is completely reversed after in vitro culture of the isolated NPCs. Together, these data indicate that the inflamed brain microenvironment sustains a non cell-autonomous dysfunction of the endogenous CNS stem cell compartment and challenge the potential efficacy of proposed therapies aimed at mobilizing endogenous precursors in chronic inflammatory brain disorders.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570715/pdf/Terms of Use
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