Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medial preoptic nucleus (MPN) is the major nucleus of the preoptic area (POA), a hypothalamic area involved in the regulation of body-temperature. Injection of capsaicin into this area causes hypothermia in vivo. Capsaicin also causes glutamate release from hypothalamic slices. However, no data are available on the effect of capsaicin on synaptic transmission within the MPN. Here, we have studied the effect of exogenously applied capsaicin on spontaneous synaptic activity in hypothalamic slices of the rat. Whole-cell patch-clamp recordings were made from visually identified neurons located in the MPN. In a subset of the studied neurons, capsaicin enhanced the frequency of spontaneous glutamatergic EPSCs. Remarkably, capsaicin also increased the frequency of GABAergic IPSCs, an effect that was sensitive to removal of extracellular calcium, but insensitive to tetrodotoxin. This suggests an action of capsaicin at presynaptic GABAergic terminals. In contrast to capsaicin, the TRPV4 agonist 4alpha-PDD did not affect GABAergic IPSCs. Our results show that capsaicin directly affects synaptic transmission in the MPN, likely through actions at presynaptic terminals as well as on projecting neurons. Our data add to the growing evidence that capsaicin receptors are not only expressed in primary afferent neurons, but also contribute to synaptic processing in some CNS regions.
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PMID:Capsaicin augments synaptic transmission in the rat medial preoptic nucleus. 1586 12

Traumatic brain injury (TBI) initiates a cascade of cellular and molecular responses including both pro- and anti-inflammatory. Although post-traumatic hypothermia has been shown to improve outcome in various models of brain injury, the underlying mechanisms responsible for these effects have not been clarified. In this study, inflammation cDNA arrays and semi-quantitative RT-PCR were used to detect genes that are differentially regulated after TBI. In addition, the effect of post-traumatic hypothermia on the expression of selective genes was also studied. Rats (n = 6-8 per group) underwent moderate fluid-percussion (F-P) brain injury with and without hypothermic treatment (33 degrees C/3 h). RNA from 3-h or 24-h survival was analyzed for the expression of IL1-beta, IL2, IL6, TGF-beta2, growth-regulated oncogene (GRO), migration inhibitory factor (MIF), and MCP (a transcription factor). The interleukins IL-1beta, IL-2, and IL-6 and TGF-beta and GRO were strongly upregulated early and transiently from 2- to 30-fold over sham at 3 h, with normalization by 24 h. In contrast, the expressions of MIF and MCP were both reduced by TBI compared to sham. Post-traumatic hypothermia had no significant effect on the acute expression of the majority of genes investigated. However, the expression of TGF-beta2 at 24 h was significantly reduced by temperature manipulation. The mechanism by which post-traumatic hypothermia is protective may not involve a general genetic response of the inflammatory genes. However, specific genes, including TGF-beta2, may be altered and effect cell death mechanisms after TBI. Hypothermia differentially regulates certain genes and may target more delayed responses underlying the secondary damage following TBI.
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PMID:The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat. 1592 84

We have demonstrated that therapeutic administration of L-arginine (L-arg) (120 mg/kg) at +2 h of whole body hyperthermia (WBH) could rescue the mice from heatstroke-induced death. Studies were undertaken to elucidate the role of L-arg in the immunomodulation of the heat-stressed mice. Administration of L-arginine (L-arg), (120 mg/kg, i.p.), at +2 h of WBH, rescued the mice from heat-induced death and reduced the hypothermia. At +4 and +24 h of WBH, levels of IL-1beta, IFN-gamma, nitrite, TNF-alpha, IL-4, TGF-beta1, inducible form of nitric oxide synthase (iNOS), and corticosterone significantly increased compared to the sham group. The elevated levels of Th(1) cytokines, namely TNF-alpha, IL-1beta, IFN-gamma, nitrite, and iNOS, decreased significantly both at +4 and +24 h of WBH, following L-arg administration. However, L-arg administration did not reduce the increased levels of Th(2) cytokines, namely IL-4 and TGF-beta1, in WBH mice at +4 h of WBH. L-arg administration significantly increased the levels of Th(2) cytokines at +24 h of WBH, compared to the saline-treated WBH mice. L-arg administration significantly increased both the splenic and hepatic arginase activity at +4 and +24 h of WBH compared to the saline-treated WBH mice. L-NAME treatment at +2 h of WBH and anti-TGF-beta antibody treatment at 0 h of WBH significantly increased the mortality compared to the saline-treated WBH mice. Altered liver histopathology was attenuated following the administration of L-arg at +2 h of WBH. These results suggest that therapeutic administration of L-arg at appropriate concentration and time attenuates the acute inflammatory response, leading to the rescue of mice from heatstroke.
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PMID:Arginine metabolic pathways determine its therapeutic benefit in experimental heatstroke: role of Th1/Th2 cytokine balance. 1676 19