How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli

There are exciting new developments regarding the molecular mechanisms invo lved in the Influence of circulating proinflammatory molecules within cells of the blood-brain barrier (BBB) during systemic immune challenges. These molecules, when present in the circulation, have the ability to trigger a s eries of events In cascade, leading to either the mitogen-activated protein (MAP) kinases/nuclear factor kappa B (NF-kappa B) or the janus kinase (JAK )/signal transducer and activator of transcription (STAT) transduction path ways in vascular-associated cells of the central nervous system (CNS). The brain blood vessels exhibit both constitutive and induced expression of rec eptors for different proinflammatory ligands that have the ability to stimu late these signaling molecules. Depending on the challenges and the cytokin es involved, the transduction signal(s) solicited in cells of the BBB may o rient the neuronal activity in a very specific manner in activating the tra nscription and production of soluble factors, such as prostaglandins (PGs). It is interesting to note that cytokines as well as systemic localized inf lammation stimulate the cells of the BBB In a nonselective manner (i.e., wi thin both large blood vessels and small capillaries across the brain). This nonselectivity raises several questions with regard to the localized neuro nal activation induced by different experimental models of inflammation and cytokines. It is possible that the selectivity of the neuronal response Is a consequence of the fine interaction between nonparenchymal synthesis of soluble mediators and expression of specific receptors for these ligands, w ithin parenchymal elements of different brain nuclei, This review will pres ent the recent developments on this concept and the mechanisms that take pl ace in cells of the BBB, which lead to the neuronal circuits involved in re storing the body's homeostasis during systemic immunogenic challenges. The induction of fever, the hypothalamic-pituitary adrenal (HPA) axis, and othe r autonomic functions are among the physiological outcomes necessary far th e protection of the mammalian organism in the: presence of foreign material .