The relevance of astrogliosis remains controversial, especially with respect to the beneficial or detrimental influence of reactive astrocytes on CNS recovery. This dichotomy can be resolved if the mediators of astrogliosis are identified. We have measured the levels of transcripts encoding inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α, which are considered to be microglia/macrophage cytokines. The elevations preceded, or occurred concomitantly with, the rise in glial fibrillary acidic protein mRNA, an early manifestation of astrogliosis. In neonatal mice, IL-1 and TNF-α mRNA were elevated to a greater extent by an NC-implant injury, which produced astrogliosis, than after an NC-stab, with minimal astrogliosis. We determined whether endogenous interferon (IFN)-γ could be responsible for the observed increases in IL-1 and TNF-α, because IFN-γ is a potent microglia/macrophage activator, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-γ was demonstrated by three lines of evidence. First, no increase in IFN-γ transcripts could be found at injury. Second, the administration of a neutralizing antibody to IFN-γ did not attenuate astrogliosis. Third, in IFN-γ knockout adult mice, astrogliosis and increases in levels of IL-1α and TNF-α were induced rapidly by injury. The marked elevation of inflammatory cytokines is discussed in the context of astrogliosis and general CNS recovery.

Este artículo propone una interpretacíon religiosa y no astronómica de los biomorfos y geoglifos de la pampa de Nasca. Los dibujos habrian sido creados para advertir al dios alado y volador Uamado Kón que había arribado a Nasca donde le aguardaban sus sacerdotes y sus fieles.

No abstract

fibrillary acidic protein (GFAP) is an intermediate filament specifically expressed In gUM cells which conlributes to and malnlains the stability of the astrocyte's cytoskeleton. We have previously observed that GFAP expression is reduced in rnalignant glial tmnors, and that the up-regulation of GFAP expression affects glial cell proliferation and tumorigenicity (Cancer Res. 53:3624, 1993). To determine how the transcription of the GFAP is repressed in malignant glial tumors, we looked for genomle rearrangements of the GFAP gene by Southern analysis, but none was found. However, we have shown for the first time that the GFAP gene was hyper-methylated in five GFAP negative glioma cells. This hyper-methylalion was also detected in other GFAP negative non-glial cells. Both hyper-and hypo-methylation of DNA have been shown in a variety of tumor types to be important [actors affecting gene transcription. This methylation-mediated repression of transcription is thought to be a candidate mechanism for the decreased expression of several tumor suppressor genes, and may also be one mechanism by which there is loss of GFAP gene expression in malignant gliomas (Supported by NCI Canada).