Induction of inhibitory factor kappa B alpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: An in situ hybridization histochemistry study in the rat

In this study we investigate the mRNA expression of inhibitory factor kappa B alpha (I kappa B alpha) in cells of the rat brain induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), I kappa B controls the activity of nuclear factor kappa B, which regulates the transcription of many immune signal molecules, The detection of I kappa B induction, therefore, would reveal the extent and the cellular location of brain-derived immune molecules in response to peripheral immune challenges, Low levels of I kappa B alpha mRNA were found in the large blood vessels and in circumventricular organs (CVOs) of saline-injected control animals, After an i.p. LPS injection (2.5 mg/kg), dramatic induction of I kappa B alpha mRNA occurred in four spatio-temporal patterns, Induced signals were first detected at 0.5 hr in the lumen of large blood vessels and in blood vessels of the choroid plexus and CVOs, Second, at 1-2 hr, labeling dramatically increased in the CVOs and choroid plexus and spread to small vascular and glial cells throughout the entire brain; these responses peaked at 2 hr and declined thereafter, Third, cells of the meninges became activated at 2 hr and persisted until 12 hr after the LPS injection, Finally, only at 12 hr, induced signals were present in ventricular ependyma, Thus, I kappa B alpha mRNA is induced in brain after peripheral LPS injection, beginning in cells lining the blood side of the blood-brain barrier and progressing to cells inside brain, The spatiotemporal patterns suggest that cells of the blood-brain barrier synthesize immune signal molecules to activate cells inside the central nervous system in response to peripheral LPS, The cerebrospinal fluid appears to be a conduit for these signal molecules.