The Role of the Vagus Nerve in Cytokine-to-Brain Communication
ABSTRACT Peripheral interleukin-1 beta (IL-beta) and inflammatory stimuli that induce the synthesis and release of IL-1 beta produce a variety of central nervous system responses. Most proposals designed to explain how peripheral IL-1 beta influences the CNS have focused on blood-borne routes of communication. We will review data that indicate that at least some of the CNS response to peripheral IL-1 beta are instead mediated by a neural route of communication between the periphery and the CNS. IL-1 beta activates afferent vagal fibers that terminate in the nucleus tractus solitarius, and communication via the vagus is responsible for much of the hyperalgesia, fever, anorexia, taste aversions, increased levels of plasma corticosteroid, and brain norepinephrine changes produced by intraperitoneal injections of IL-1 beta and LPS. Data extending this analysis to TNF-alpha and intravenous routes will be described.
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ABSTRACT: Microglia, the resident immune cells of the brain parenchyma, are highly responsive to tissue injury. Following cell damage, microglial processes redirect their motility from randomly scouting the extracellular space to specifically reaching toward the compromised tissue. While the cell morphology aspects of this defense mechanism have been characterized, the intracellular events underlying these responses remain largely unknown. Specifically, the role of intracellular Ca(2+) dynamics has not been systematically investigated in acutely activated microglia due to technical difficulty. Here we used live two-photon imaging of the mouse cortex ubiquitously expressing the genetically encoded Ca(2+) indicator GCaMP5G and fluorescent marker tdTomato in central nervous system microglia. We found that spontaneous Ca(2+) transients in microglial somas and processes were generally low (only 4% of all microglia showing transients within 20 min), but baseline activity increased about 8-fold when the animals were treated with LPS 12 h before imaging. When challenged with focal laser injury, an additional surge in Ca(2+) activity was observed in the somas and protruding processes. Notably, coherent and simultaneous Ca(2+) rises in multiple microglial cells were occasionally detected in LPS-treated animals. We show that Ca(2+) transients were pre-dominantly mediated via purinergic receptors. This work demonstrates the usefulness of genetically encoded Ca(2+) indicators for investigation of microglial physiology.Frontiers in Molecular Neuroscience 05/2015; 8. DOI:10.3389/fnmol.2015.00012
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ABSTRACT: This study investigated the effect of capsaicin (the active principle of hot red pepper and a sensory excitotoxin) on oxidative stress after systemic administration of the endotoxin lipopolysaccharide (100 μg/kg, i.p.) in rats. Capsaicin (15, 150 or 1,500 μg/kg; 10, 100 or 400 μg/mL) was given via intragastric (i.g.) or intraperitoneal (i.p.) routes at time of endotoxin administration. Rats were killed 4 h later. Malondialdehyde (MDA) and reduced glutathione (GSH) were measured in brain, liver, and lungs. Alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase (ALP), nitric oxide, and glucose were measured in serum. In addition, histopathological examination of liver tissue was performed. In LPS-treated rats, hepatic GSH increased significantly by 40.8% after i.p. capsaicin at 1,500 μg/kg. Liver MDA increased significantly by 32.9% after the administration of i.g. capsaicin at 1,500 μg/kg and by 27.8 and 37.6% after the administration of i.p. capsaicin at 150 and 1,500 μg/kg, respectively. In lung tissue, both MDA and GSH were decreased by capsaicin administration. MDA decreased by 19-20.8% after i.g. capsaicin and by 17.5-23.2% after i.p. capsaicin (150-1,500 μg/kg), respectively. GSH decreased by 39.3-64.3% and by 35.7-41.1% after i.g. or i.p. capsaicin (150-1,500 μg/kg), respectively. Brain GSH increased significantly after the highest dose of i.g. or i.p. capsaicin (by 20.6 and 15.9%, respectively). The increase in serum ALT and ALP after endotoxin administration was decreased by oral or i.p. capsaicin. Serum nitric oxide showed marked increase after LPS injection, but was markedly decreased after capsaicin (1,500 μg/kg, i.p.). Serum glucose increased markedly after the administration of LPS, and was normalized by capsaicin treatment. It is suggested that in the presence of mild systemic inflammation, acute capsaicin administration might alter oxidative status in some tissues and exert an anti-inflammatory effect. Capsaicin exerted protective effects in the liver and lung against the LPS-induced tissue damage.Inflammopharmacology 11/2011; 20(4):207-17. DOI:10.1007/s10787-011-0101-9
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ABSTRACT: Many lung and central nervous system disorders require robust and appropriate physiological responses to assure adequate breathing. Factors undermining the efficacy of ventilatory control will diminish the ability to compensate for pathology, threatening life itself. Although most of these same disorders are associated with systemic and/or neuroinflammation, and inflammation affects neural function, we are only beginning to understand interactions between inflammation and any aspect of ventilatory control (e.g. sensory receptors, rhythm generation, chemoreflexes, plasticity). Here we review available evidence, and present limited new data suggesting that systemic (or neural) inflammation impairs two key elements of ventilatory control: chemoreflexes and respiratory motor (versus sensory) plasticity. Achieving an understanding of mechanisms whereby inflammation undermines ventilatory control is fundamental since inflammation may diminish the capacity for natural, compensatory responses during pathological states, and the ability to harness respiratory plasticity as a therapeutic strategy in the treatment of devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.Respiratory Physiology & Neurobiology 06/2011; 178(3):482-9. DOI:10.1016/j.resp.2011.06.017 · 1.97 Impact Factor