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.

Th1 Polarization of T Cells Injected into the Cerebrospinal Fluid Induces Brain Immunosurveillance

“…However, similar to human AD patients immunized with Ab (Elan's trial), the immunized mice develop meningoencephalitis presumably due to T cell activation at the perivascular/subarachnoid space prior to crossing the glia limitans. Similar effects of T cell activation at the brain vasculature were also described in MS (14) and are likely to impair the brain-endogenous capacity for cell renewal and repair (48,49). In contrast, because activated T cells in the current study were injected directly into the lateral ventricle, no further activation was required prior to crossing the epithelial layer or the vasculature's glia limitans into the brain parenchyma, and, as such, the injected cells induced neither significant vascular pathology nor cellular apoptosis, but instead, similar to previous studies demonstrating the positive effects of T cells and IFN-g on neurogenesis (24, 27, 50, 51), slightly enhanced hippocampal neurogenesis in an age-dependent manner.…”

Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation

“…Mouse neural precursor cells (NPCs), donated by Dr. Stefano Pluchino (University of Cambridge, U.K.), were prepared and cultured as described 14.…”

Osteogenic potential of periodontal ligament stem cells are unaffected after exposure to lipopolysaccharides

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