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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothermia has been demonstrated to be an effective neuroprotective strategy in a number of models of ischaemic and excitotoxic neurodegeneration in vitro and in vivo. Reduced glutamate release and free radical production have been postulated as potential mechanisms underlying this effect but no definitive mechanism has yet been reported. In the current study, we have used oxygen-glucose deprivation in organotypic hippocampal slice cultures as an in vitro model of cerebral ischaemia. When assessed by propidium iodide fluorescence, reducing the temperature during oxygen-glucose deprivation to 31-33 degrees C was significantly neuroprotective but this effect was lost if the initiation of hypothermia was delayed until the post-insult recovery period. The neuroprotective effects of hypothermia were associated with a significant decrease in both nitric oxide production, as assessed by 3-amino-4-aminomethyl-2',7'-difluorofluorescein fluorescence, and superoxide formation. Further, hypothermia significantly attenuated NMDA-induced nitric oxide formation in the absence of hypoxia/hypoglycaemia. We conclude that the neuroprotective effects of hypothermia are mediated through a reduction in nitric oxide and superoxide formation and that this effect is likely to be downstream of NMDA receptor activation.
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PMID:Intraischaemic hypothermia reduces free radical production and protects against ischaemic insults in cultured hippocampal slices. 1544 66

In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23 degrees C (T(rec) 23 degrees C) during C-H-R exposure and its recovery to T(rec) 37 degrees C at normal atmospheric pressure and 32 +/- 1 degrees C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining T(rec) 23 degrees C and T(rec) 37 degrees C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining T(rec) 23 degrees C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (T(rec) 37 degrees C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attaining T(rec) 23 degrees C during C-H-R exposure and on recovery to T(rec) 37 degrees C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.
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PMID:Anti-stress and Adaptogenic Activity of l-Arginine Supplementation. 1584 Dec 83

Multisystem organ failure represents a major cause of mortality in intestinal ischemia and reperfusion (I/R), and oxidative stress plays a key role in its pathogenesis. Hypothermia is beneficial in I/R injury, but its effects on systemic oxidative stress have not been elucidated. The aim of this study was to evaluate the effects of moderate hypothermia on systemic oxidative stress after intestinal I/R injury. Anaesthetized adult rats (n = 10 per group) underwent 60 min of intestinal ischemia followed by 120 min of reperfusion or sham operation at normothermia (36 degrees C-38 degrees C) or moderate hypothermia (30 degrees C-32 degrees C). At sacrifice, ileum, liver, lungs, and kidneys were removed to determine the concentration of malondialdehyde (a marker of lipid peroxidation), reduced and oxidized glutathione (a major endogenous antioxidant), and glutathione redox state. Plasma malondialdehyde and nitrate plus nitrite (reflecting nitric oxide production) were also analyzed. A marked elevation of malondialdehyde was observed after I/R at normothermia in plasma, ileum, and lungs; however, hypothermia during I/R prevented this increase. I/R at normothermia caused a profound decrease in reduced glutathione and glutathione redox state in the ileum, but this was not observed in I/R at hypothermia. Interestingly, hypothermia increased glutathione content of control intestine. Nitric oxide production was increased only in normothermic I/R animals. Moderate hypothermia attenuates systemic oxidative stress associated with experimental intestinal I/R in an animal model by decreasing lipid peroxidation in plasma, ileum, lungs, and kidneys, by preventing the depletion of gut glutathione, and by reducing systemic nitric oxide production. However, whether these effects persist after rewarming is unknown.
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PMID:Moderate hypothermia protects against systemic oxidative stress in a rat model of intestinal ischemia and reperfusion injury. 1604 87

Hypothermia is often associated with compromised host defenses and infection. Deteriorations of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. We have previously shown that mild hypothermia modifies cytokine production by peripheral blood mononuclear cells. In this study, the effects of hypothermia on the monocytic production of several cytokines and nitric oxide (NO) were determined. Monocytes obtained from 10 healthy humans were cultured with lipopolysaccharide (LPS) under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions for 48 hours. We performed flow cytometric analysis for simultaneous measurement of interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha in culture supernatants. NO production was quantified as accumulation of nitrite in the medium by a colorimetric assay. Compared with normothermia, mild hypothermia raised the levels of IL-1beta, IL-6, IL-12p70, and TNF-alpha produced by monocytes stimulated with LPS. On calculating the ratios of these elevated cytokines to IL-10, however, only IL-12p70/IL-10 and TNF-alpha/IL-10 ratios were significantly elevated under hypothermic conditions. In contrast, hypothermia did not affect NO production. This study demonstrates that mild hypothermia affects the balance of cytokines produced by monocytes, leading to a pro-inflammatory state. Specifically, monocytic IL-12 and TNF-alpha appear to be involved in the immune alterations observed in mild hypothermia. However, the clinical significance of these phenomena remains to be clarified.
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PMID:Mild hypothermia promotes pro-inflammatory cytokine production in monocytes. 1636 38

Among the anesthetics influencing the nitric oxide (NO) pathway, ketamine is widely reported in the literature. We researched the variations in blood physiological parameters following ketamine/xylazine- or pentobarbital-induced anesthesia, with particular emphasis on plasmatic NO levels and oxidative stress-related factors. The effects of ketamine on hepatic blood flow during deep hypothermia were also examined. Adult male Sprague-Dawley rats were anesthetized intraperitoneally with ketamine/xylazine or with sodium pentobarbital. Animals underwent serial blood extraction to analyze acid-base balance and lactate levels in blood, as well as NO, MDA, SH groups, and AST levels in plasma samples. We demonstrated that ketamine leads to increased plasmatic NO levels, induces metabolic acidosis, and causes oxidative damage, though without reaching hepatic toxicity. When experimental hypothermia was induced, ketamine affected hepatic blood flow. Based on these results, we suggest that studies on physiological processes involving NO should exercise caution if anesthesia is induced by ketamine.
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PMID:Nitric oxide induced by ketamine/xylazine anesthesia maintains hepatic blood flow during hypothermia. 1638 21

Microglial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, but the mechanisms involved are unclear. To investigate the microglial-neuronal interactions, we used the murine BV-2 microglial cell line and the human neuronal-like SK-N-SH neuroblastoma cell line in a co-culture system that enabled proximity-dependent interaction and communication, a trans-well system that allowed proximity-independent communication through diffusible molecules only, and a conditioned media system through which no proximity-dependent interactions or cell-to-cell communication is possible. Activation of BV-2 cells with lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) decreased viability of the BV-2 cells alone and in co-cultures with SK-N-SH cells, but not SK-N-SH cells grown alone. In contrast, activation of BV-2 cells in the trans-well and conditioned media system did not have any effect on the viability of SK-N-SH cells, suggesting that microglia must be in close proximity to the neural cells to elicit cytotoxicity. To determine the molecules involved in proximity-dependent cell death, inhibitors of microglial activation were investigated. Only the specific inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea, and hypothermia, which is known to suppress microglial iNOS expression, prevented cell death after LPS/IFN-gamma activation. These results suggest that activated microglia release nitric oxide that is, at least partially, responsible for proximity-dependent microglial-mediated neural toxicity.
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PMID:Microglia induce neural cell death via a proximity-dependent mechanism involving nitric oxide. 1656 33

The role of nitric oxide (NO) production in delta opioid receptor-induced hypothermia has not been reported. The present study investigated the effect of nitric oxide synthase (NOS) inhibitors on the hypothermic effect of (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80), a nonpeptide delta opioid agonist. SNC-80 (35 mg/kg, i.p.) administered to rats caused a significant hypothermia. N-nitro-L-arginine methyl ester (L-NAME) (10, 25 and 50 mg/kg, i.p.), a NOS inhibitor, and 7-nitroindazole (7-NI) (5 and 10 mg/kg, i.p.), a neuronal NOS inhibitor, were ineffective. For combined administration, L-NAME (50 mg/kg, i.p.) or 7-NI (10 mg/kg, i.p.) attenuated SNC-80-evoked hypothermia. To determine the involvement of central NOS, L-NAME (0.25, 0.5 and 1 mg/rat) was administered i.c.v. 30 min prior to SNC-80 (35 mg/kg, i.p.). Experiments revealed that L-NAME (1 mg/rat, i.c.v.) attenuated SNC-80-induced hypothermia. The present data demonstrate that central NO production is necessary for delta opioid receptor-induced hypothermia.
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PMID:Nitric oxide synthase mediates delta opioid receptor-induced hypothermia in rats. 1656 19

We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemia by regulating vasopressin (AVP) release. Wild-type (WT) and iNOS knockout mice (KO) were intraperitoneally injected with either saline or Escherichia coli lipopolysaccharide (LPS) 10.0 mg/kg in a final volume of 0.02 mL. Body temperature was measured continuously by biotelemetry during 24 h after injection. Three hours after LPS administration, we observed a significant drop in body temperature (hypothermic response) in WT mice, which remained until the seventh hour, returning then close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the fourth hour of LPS administration; however, the hypothermic response persisted until the end of the 24 h of the experiment. The pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Et-Tyr2, Val4, Arg8-Vasopressin, an AVP V1 receptor antagonist (10 microg/kg) administered intraperitoneally, abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this experimental model. In conclusion, our data suggest that the iNOS isoform plays a role in LPS-induced hypothermia, apparently through the regulation of AVP release.
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PMID:Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia. 1671 35

Mild hypothermia is one of the most robust neuroprotectant studied in the laboratory to date. The reasons for this protective effect are likely multifactorial, but work from our laboratory and others have shown that this protection is associated with remarkable suppression of the inflammatory response that accompanies brain ischemia. Consistently, laboratories have shown that small decreases in brain temperature to 30-34 degrees C result in reduced inflammatory cell infiltrate, less microglial activation, and reduction of a variety of inflammatory mediators such as nitric oxide, inflammatory cytokines and superoxide. Nuclear factor-kappaB (NFkappaB) is a transcription factor that is activated after cerebral ischemia. NFkappaB activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. Our laboratory has shown that hypothermia decreases NFkappaB translocation and binding activity, by affecting NFkappaB regulatory proteins. Mild hypothermia appears to suppress phosphorylation of NFkappaB's inhibitory protein (IkappaB-alpha) by decreasing expression and activity of IkappaB kinase-gamma (IKK). As a consequence, hypothermia suppressed gene expression of two NFkappaB target genes, inducible nitric oxide synthase and TNF-alpha. These data suggest that the protective effect of hypothermia on cerebral injury is, in part, related to NFkappaB inhibition due to decreased activity of IKK.
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PMID:Influence of hypothermia on post-ischemic inflammation: role of nuclear factor kappa B (NFkappaB). 1675 Aug 72

Hypothermia is often associated with compromised host defenses and infection. Deteriorations of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. We have previously shown that mild hypothermia modifies cytokine production by peripheral blood mononuclear cells. In this study, the effects of hypothermia on the monocytic production of several cytokines and nitric oxide (NO) were determined. Monocytes obtained from 10 healthy humans were cultured with lipopolysaccharide (LPS) under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions for 48 hours. We performed flow cytometric analysis for simultaneous measurement of interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-alpha in culture supernatants. NO production was quantified as accumulation of nitrite in the medium by a colorimetric assay. Compared with normothermia, mild hypothermia raised the levels of IL-1beta, IL-6, IL-12p70, and TNF-alpha produced by monocytes stimulated with LPS. On calculating the ratios of these elevated cytokines to IL-10, however, only IL-12p70/IL-10 and TNF-alpha/IL-10 ratios were significantly elevated under hypothermic conditions. In contrast, hypothermia did not affect NO production. This study demonstrates that mild hypothermia affects the balance of cytokines produced by monocytes, leading to a pro-inflammatory state. Specifically, monocytic IL-12 and TNF-alpha appear to be involved in the immune alterations observed in mild hypothermia. However, the clinical significance of these phenomena remains to be clarified.
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PMID:Mild hypothermia promotes pro-inflammatory cytokine production in monocytes. 1679 46


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