Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines @entity635 and XXXX .

@entity558 @entity1992 @entity64 @entity131 @entity1750 @entity19 @entity635 @entity1579 @entity15891 @entity281 @entity179 @entity637
Microgliosis and astrogliosis are standard pathological features of @entity179 . Microglia are primed by chronic @entity179 such that toll-like receptor agonists, such as @entity558 , drive exaggerated cytokine responses on this background. However, sterile inflammatory insults are more common than direct CNS @entity281 in the degenerating brain and these insults drive robust @entity635 and @entity637 responses. It is unclear whether these pro-inflammatory cytokines can directly induce exaggerated responses in the degenerating brain. We hypothesized that glial cells in the hippocampus of animals with @entity179 ( @entity1579 ) would display exaggerated responses to central cytokine challenges. @entity637 or @entity635 were administered intrahippocampally to ME7-inoculated @entity19 and normal brain homogenate-injected (NBH) controls. Both @entity635 and @entity637 produced much more robust @entity635 synthesis in ME7 than in NBH animals and this occurred exclusively in microglia. However, there was strong nuclear localization of the NFkB subunit @entity1992 in the astrocyte population, associated with marked astrocytic synthesis of the chemokines @entity15891 and @entity1750 in response to both cytokine challenges in ME7 animals. Conversely, very limited expression of these chemokines was apparent in NBH animals similarly challenged. Thus, astrocytes are primed in the degenerating brain to produce exaggerated chemokine responses to acute stimulation with pro-inflammatory cytokines. Furthermore, this results in markedly increased neutrophil, T-cell, and monocyte infiltration in the diseased brain. These data have significant implications for acute sterile inflammatory insults such as @entity64 and @entity131 occurring on a background of aging or @entity179 .
