Peptides
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Relationship between plasma leptin levels and clinical outcomes of pediatric traumatic brain injury.
High plasma leptin level has been associated with mortality after adult intracerebral hemorrhage. The present study was undertaken to investigate the plasma leptin concentrations in children with traumatic brain injury and to analyze the correlation of leptin with pediatric traumatic brain injury outcome. Plasma leptin concentration of eighty-nine healthy children and 142 children with acute severe traumatic brain injury was measured by enzyme-linked immunosorbent assay. ⋯ A receiver operating characteristic curve analysis showed plasma leptin level better predicted 6-month mortality and unfavorable outcome. The prognostic value of leptin was similar to that of Glasgow Coma scale score for 6-month clinical outcomes. Thus, plasma leptin level represents a novel biomarker for predicting 6-month clinical outcome in children with traumatic brain injury.
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Brain inflammation is sustained by chronic activation of microglia and the over-production of pro-inflammatory cytokines and nitric oxide (NO), which in turn can be highly neurotoxic. Microglial activation can be regulated by neuropeptides such as bradykinin (BK) and other members of the kinin family. Kinins are well known inflammatory regulators outside the CNS. ⋯ In addition, all kinin agonists reduced the expression of iNOS and TNF-α protein and mRNA levels in LPS-stimulated BV2 cells. Also, while LPS activated the nuclear factor-κB (NF-κB) pathway, BK inhibited NF-κB activation by preventing degradation of the κB protein (IκB) inhibitor, abolishing translocation of p65 and p50 subunits to the nucleus and inhibiting NF-κB transcription activity. These results suggest a role for bradykinin in modulation of glial inflammation, as evidenced by attenuation of NO and TNF-α synthesis pathways in activated microglial cells.
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The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity-diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9-36)amide and GIP(3-42), respectively. Therefore, the present study investigated effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive function and hippocampal synaptic plasticity in mice with diet-induced obesity and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide, GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any changes in bodyweight, non-fasting plasma glucose and plasma insulin concentrations or glucose tolerance compared with high-fat saline controls. ⋯ Administration of the truncated metabolites did not alter general behavior in an open field test or learning and memory ability as recorded during an object recognition test. High-fat mice exhibited a significant impairment in hippocampal long-term potentiation (LTP) which was not affected by treatment with incretin metabolites. These data indicate that incretin metabolites do not influence locomotor activity, cognitive function and hippocampal synaptic plasticity when administered at pharmacological doses to mice fed a high-fat diet.
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The neuropeptide Substance P (SP), that has a high affinity for the neurokinin 1 (NK1) receptor, is involved in modulation of pain transmission. Although SP is thought to have excitatory actions and promote nociception in the spinal cord, the peptide induces analgesia at the supraspinal level. The aim of this study was to evaluate the role of supraspinal SP and the NK1 receptor in inflammatory pain induced by injection of carrageenan in the hind paw of the rat. ⋯ This SP-induced analgesia was significantly reduced by administration of the opioid antagonist naloxone (3mg/kg s.c.). This reduction occurred when SP was administered either before or after the carrageenan injection. These results suggest a significant antinociceptive role for SP and the NK1 receptor in inflammatory pain at the supraspinal level, possibly through the release of endogenous opioids.
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Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). Recently, the NPSR ligand [(t)Bu-D-Gly(5)]NPS was generated and in vitro characterized as a pure antagonist at the mouse NPSR. In the present study the pharmacological profile of [(t)Bu-D-Gly(5)]NPS has been investigated. [(t)Bu-D-Gly(5)]NPS activity was evaluated in vitro in the calcium mobilization assay at the rat NPSR and in vivo in the locomotor activity and righting reflex tests in mice and in the elevated plus maze and defensive burying assays in rats. ⋯ Finally, [(t)Bu-D-Gly(5)]NPS (3-30 nmol) was able to completely block NPS (1 nmol) anxiolytic-like actions in rat elevated plus maze and defensive burying assays. Collectively, the present results demonstrated that [(t)Bu-D-Gly(5)]NPS behaves both in vitro and in vivo as a pure and potent NPSR antagonist. This compound represents a novel and useful tool for investigating the pharmacology and neurobiology of the NPS/NPSR system.