Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood-brain barrier.

摘要: Tumor necrosis factor is a potent activator of myeloid cells, which acts via two cell-surface receptors, the p55 and p75 tumor receptors. The present study describes cellular distribution both receptor messenger RNAs across rat brain under basal conditions in response to systemic injection with bacterial endotoxin lipopolysaccharide recombinant factor-alpha. Time-related induction RNA encoding c-fos, cyclo-oxygenase-2 enzyme inhibitory kappa B alpha was assayed as an index activated neurons cells microvasculature by intravenous factor-alpha challenge. effect proinflammatory cytokine on hypothalamic-pituitary-adrenal axis determined measuring transcriptional activity corticotropin-releasing plasma corticosterone levels. Constitutive expression detected circumventricular organs, choroid plexus, leptomeninges, ependymal lining ventricular walls along blood vessels, whereas transcript barely detectable conditions. Immunogenic insults caused up-regulation receptors barrier-associated structures, well over event that associated robust activation microvasculature. Indeed, provoked rapid transient transcription within blood-brain barrier, dual-labeling technique provided anatomical evidence endothelium capillaries expressed alpha. Circulating also rapidly stimulated c-fos nuclei involved autonomic control, including bed nucleus stria terminalis, paraventricular hypothalamus, central amygdala, solitary tract ventrolateral medulla. A delayed mRNA organum vascularis lamina subfornical organ, median eminence area postrema. hypothalamus exhibited primary sharp increase levels 1h after administration. Taken together, these data provide most abundant nervous system structures. has ability directly activate brain's large vessels small capillaries, may produce soluble molecules (such prostaglandins) vehicle signal through parenchymal elements. pattern c-fos-inducible suggests complex neuronal circuits solicited neuroendocrine corticotroph axis, key physiological for appropriate control inflammatory response.