title: Persistent inflammation alters the function of the endogenous brain stem cell compartment.
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.
authors.affiliation: Neuroimmunology Unit, DIBIT, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pluchino
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
authors.forename: Jaime
authors.initials: J
authors.lastname: Imitola
authors.forename: Michela
authors.initials: M
authors.lastname: Deleidi
authors.forename: Clara
authors.initials: C
authors.lastname: Alfaro-Cervello
authors.forename: Giuliana
authors.initials: G
authors.lastname: Salani
authors.forename: Cristina
authors.initials: C
authors.lastname: Porcheri
authors.forename: Elena
authors.initials: E
authors.lastname: Brambilla
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavasinni
authors.forename: Andrea
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino