How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli

Abstract

There are exciting new developments regarding the molecular mechanisms involved 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 series of events in cascade, leading to either the mitogen-activated protein (MAP) kinases/nuclear factor kappa B (NF-kappaB) or the janus kinase (JAK)/signal transducer and activator of transcription (STAT) transduction pathways in vascular-associated cells of the central nervous system (CNS). The brain blood vessels exhibit both constitutive and induced expression of receptors for different proinflammatory ligands that have the ability to stimulate these signaling molecules. Depending on the challenges and the cytokines involved, the transduction signal(s) solicited in cells of the BBB may orient the neuronal activity in a very specific manner in activating the transcription and production of soluble factors, such as prostaglandins (PGs). It is interesting to note that cytokines as well as systemic localized inflammation stimulate the cells of the BBB in a nonselective manner (i.e., within both large blood vessels and small capillaries across the brain). This nonselectivity raises several questions with regard to the localized neuronal 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 within parenchymal elements of different brain nuclei. This review will present the recent developments on this concept and the mechanisms that take place in cells of the BBB, which lead to the neuronal circuits involved in restoring the body's homeostasis during systemic immunogenic challenges. The induction of fever, the hypothalamic-pituitary adrenal (HPA) axis, and other autonomic functions are among the physiological outcomes necessary for the protection of the mammalian organism in the presence of foreign material.

Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function

“…Thus, the treatment of anemia and systemic inflammation should reduce endogenous stress and thereby attenuate the progression of host weight loss secondary to malignant disease, 30 although control of food intake may or may not be directly related to anemia and inflammation. [33][34][35][36][37] Little is known regarding metabolic efficiency during exercise in patients with various conditions, but our previous findings are compatible with the observation of less efficient oxygen transport and a subsequently increased energy burden on the cardiovascular system during walking in patients with malignant disease who were experiencing anemia. 9 A simplistic explanation for observations made in weight-losing patients with malignant disease is that metabolically inefficient organisms consume more energy during periods of rest as well as periods of motion.…”

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

“…Peripheral cytokines have access to the CNS (Schiepers et al, 2005), and both IL-1b and TNF-a are expressed in the brain (Botchkina et al, 1997;Rivest et al, 2000;Sheng et al, 2001;Bette et al, 2003). Inflammatory cytokines are known to alter metabolism and release of central serotonin (5-hydroxytryptamine, 5-HT) in the CNS (Dunn, 1992;Palazzolo and Quadri, 1992;Cho et al, 1999).…”

Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

“…IL-1␤ activates pPVN CRH neurons via a direct noradrenergic pathway from the nucleus tractus solitarii (NTS) (Rivier et al, 1989). Circulating IL-1␤ binds to IL-1 receptors on brain microvessel endothelium, triggering local prostaglandin synthesis (Zhang and Rivest, 1999;Rivest et al, 2000), which excites PVN-projecting noradrenergic A2 neurons (Ericsson et al, 1994).…”