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

Perinatal hypoxic-ischaemic encephalopathy(HIE) is being studied in laboratory models that allow the delayed cascade of events triggered by the energetic insult to be examined in detail. The concept of the 'excitotoxic cascade' provides a conceptual framework for thinking about the pathogenesis of HIE. Major events in the cascade triggered by hypoxia-ischaemia include overstimulation of N-methyl-D-aspartate type glutamate receptors, calcium entry into cells, activation of calcium-sensitive enzymes such as nitric oxide synthase, production of oxygen free radicals, injury to mitochondria, leading in turn to necrosis or apoptosis. New experimental approaches to salvaging brain tissue from the effects of HIE include inhibition of neuronal nitric oxide synthase, administration of neuronal growth factors, and inhibition of the caspase enzymes that execute apoptosis. Recent experimental work suggests that these approaches may be effective during a longer 'therapeutic window' after the insult, because they are acting on events that are relatively delayed. Application of modest hypothermia may allow these agents to be neuroprotective at even longer intervals after hypoxia-ischaemia.
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PMID:Novel treatments after experimental brain injury. 1080 52

The locus coeruleus modulates the ventilatory and thermoregulatory response to hypoxia and contains nitric oxide synthase. Therefore, we examined the effects of L-NAME unilaterally microinjected into the locus coeruleus on hypoxic hyperventilation and hypothermia. Ventilation and body temperature were measured before and after microinjection of L-NAME (100 nmol/0.5 microl) into the locus coeruleus, followed by hypoxia. Control rats received microinjection of D-NAME (an inactive enantiomer of L-NAME). Under normoxia, L-NAME treatment did not affect ventilation or body temperature. D-NAME did not affect hypoxia-induced hyperventilation and hypothermia. L-NAME treatment reduced the ventilatory response to hypoxia but did not affect hypoxia-induced hypothermia. These data suggest that nitric oxide in the locus coeruleus is involved in the ventilatory response to hypoxia, exercising an inhibitory modulation on the locus coeruleus neurons, but plays no role in hypoxia-induced hypothermia.
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PMID:Role of nitric oxide in rat locus coeruleus in hypoxia-induced hyperventilation and hypothermia. 1100 81

This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) to modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(n.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH(2)), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperitoneal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-dependent antinociception not reversed by naloxone, an opioid antagonist, but inhibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c.v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothermia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions and could modulate pain transmission independently of opioids.
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PMID:Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia. 1103 7

Septic shock, a major cause of death, is characterized by a pathophysiologic increased production of nitric oxide (NO), which leads to vasodilation and myocardial toxicity. Septic Escherichia coli frequently express proteinaceous curli fibers. In this study, curliated E. coli induced high levels of NO by directly inducing type 2 nitric oxide synthase (NOS2) both in vitro and in vivo. More severe hypotension and higher plasma nitrite/nitrate levels were seen in wild type mice systemically infected with curliated E. coli than in animals infected with E. coli mutants that lacked curli proteins. Blood pressure remained stable in NOS2-deficient mice with curliated bacteria. Increased heart rates, transient hypothermia, and loss of gross activity were seen in all mice, regardless of curli expression. Study results suggest that expression of curli fibers by E. coli activates the NO/NOS2 arm of the innate immune system, which leads to a significant fall in blood pressure.
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PMID:Activation of inducible nitric oxide synthase/nitric oxide by curli fibers leads to a fall in blood pressure during systemic Escherichia coli infection in mice. 1117 Sep 87

Hypothermia is a well-known phenomenon which accompanies hypoglycemia in mammals. The present study was designed to test the hypothesis that nitric oxide (NO) plays a role in insulin-induced hypothermia. The body temperature (Tb) of awake, unrestrained rats was measured before and after systemic infusion of insulin (2U x kg(-1) x h(-1)), and intracerebroventricular administration of NG-nitro-(L)-arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor, 200 microg/1 microl). We observed a significant reduction in body temperature after insulin infusion. L-NAME alone caused no significant change in body temperature. When the two treatments were combined, no change in Tb was observed. The data indicate that NO plays a key role in insulin-induced hypothermia.
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PMID:Role of nitric oxide in insulin-induced hypothermia in rats. 1122 13

The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on morphine hyperthermia was studied in male Sprague-Dawley rats. The first series of experiments examined the effect of subcutaneous (s.c.) administration of L-NAME on the hyperthermia induced by morphine given s.c. in doses of 4 and 15 mg/kg. L-NAME, at a s.c. dose of 50 mg/kg, per se, had no influence on body temperature (T(b)). Coadministration of L-NAME (50 mg/kg, s.c.) with the higher dose of morphine (15 mg/kg, s.c.) caused a significant suppression of morphine hyperthermia during the first 30 min and then produced hypothermia. In contrast, s.c. injection of L-NAME (50 mg/kg, s.c.) failed to alter the hyperthermic response induced by the lower dose of morphine (4 mg/kg). In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hyperthermia induced by morphine given s.c. L-NAME, itself, given i.c.v. at a dose of 1 mg did not evoke any change in T(b). Intracerebroventricular administration of L-NAME (1 mg) blocked the hyperthermia induced by 15 mg/kg morphine during the first 30 min and induced a slight hypothermia but did not alter the hyperthermia induced by 4 mg/kg morphine. The results indicate that either central or peripheral NO synthesis is required for the production of hyperthermia induced by 15 mg/kg of morphine. However, NO synthesis does not seem to be involved in the hyperthermic process induced by 4 mg/kg of morphine.
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PMID:Effect of central and peripheral administration of a nitric oxide synthase inhibitor on morphine hyperthermia in rats. 1125 Dec

Nitric oxide (NO) plays a central role in the pathogenesis of bacterial meningitis. However, the role of NO produced by endothelial NO synthase (eNOS) in meningitis is still unclear. We investigated the influence of eNOS depletion on the inflammatory host response, intracranial complications, and outcome in experimental pneumococcal meningitis. Leukocyte accumulation in the cerebrospinal fluid was more pronounced in infected eNOS-deficient mice than in infected wild type mice. This effect could be attributed to an increased expression of P-selectin, macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin (IL)-1beta in the brain of infected eNOS-deficient mice. However, no differences in the cerebral expression of intercellular adhesion molecule-1, tumor necrosis factor-alpha, and IL-6 as well as of neuronal NOS and inducible NOS could be detected between infected wild type and mutant mice. In addition to enhanced leukocyte infiltration into the CSF, meningitis-associated intracranial complications including blood-brain barrier disruption and the rise in intracranial pressure were significantly augmented in infected eNOS-deficient mice. The aggravation of intracranial complications was paralleled by a worsening of the disease, as evidenced by a more pronounced hypothermia, an enhanced weight reduction, and an increased death rate. The current data indicate that eNOS deficiency is detrimental in bacterial meningitis. This effect seems to be related to an increased expression of (certain) cytokines/chemokines and adhesion molecules; thus leading to increased meningeal inflammation and, subsequently, to aggravated intracranial complications.
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PMID:Lack of endothelial nitric oxide synthase aggravates murine pneumococcal meningitis. 1170 34

1. Administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to mice produces acute hyperthermia and long-term degeneration of striatal dopamine nerve terminals. Attenuation of the hyperthermia decreases the neurodegeneration. We have investigated the mechanisms involved in producing the neurotoxic loss of striatal dopamine. 2. MDMA produced a dose-dependent loss in striatal dopamine concentration 7 days later with 3 doses of 25 mg kg(-1) (3 h apart) producing a 70% loss. 3. Pretreatment 30 min before each MDMA dose with either of the N-methyl-D-aspartate antagonists AR-R15896AR (20, 5, 5 mg kg(-1)) or MK-801 (0.5 mg kg(-1)x3) failed to provide neuroprotection. 4. Pretreatment with clomethiazole (50 mg kg(-1)x3) was similarly ineffective in protecting against MDMA-induced dopamine loss. 5. The free radical trapping compound PBN (150 mg kg(-1)x3) was neuroprotective, but it proved impossible to separate neuroprotection from a hypothermic effect on body temperature. 6. Pretreatment with the nitric oxide synthase (NOS) inhibitor 7-NI (50 mg kg(-1)x3) produced neuroprotection, but also significant hypothermia. Two other NOS inhibitors, S-methyl-L-thiocitrulline (10 mg kg(-1)x3) and AR-R17477AR (5 mg kg(-1)x3), provided significant neuroprotection and had little effect on MDMA-induced hyperthermia. 7. MDMA (20 mg kg(-1)) increased 2,3-dihydroxybenzoic acid formation from salicylic acid perfused through a microdialysis tube implanted in the striatum, indicating increased free radical formation. This increase was prevented by AR-R17477AR administration. Since AR-R17477AR was also found to have no radical trapping activity this result suggests that MDMA-induced neurotoxicity results from MDMA or dopamine metabolites producing radicals that combine with NO to form tissue-damaging peroxynitrites.
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PMID:A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') on dopamine neurones in mouse brain. 1173 48

Previous studies have shown that nitric oxide (NO) is involved in the development of rapid tolerance to the motor incoordination produced by ethanol. In order to further investigate this involvement, three experiments were undertaken using the tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by intracerebroventricular (i.c.v.) route, blocked the development of rapid tolerance to ethanol-induced motor incoordination. This effect was prevented by i.c.v. injection of L-arginine. The second experiment showed that D-arginine did not influence the blockade of tolerance produced by 7-NI. The third experiment revealed that i.c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol.
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PMID:Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol. 1184 22

We have previously shown that Escherichia coli O111:B4 serotype lipopolysaccharide (LPS) produced a dual change in rectal temperature (Tb), in which hypothermia preceded fever at subthermoneutral ambient temperature (Tamb; 24-26 degrees C) in rats. In this study, the characteristics of the initial hypothermic response were evaluated. Hypothermia was significant when LPS (50 microg/kg, i.p.) was injected at thermoneutral Tamb (30 degrees C). There was no heat loss through tail skin during hypothermia. The open field activity of the rats did not change during this period. However, serum levels of tumor necrosis factor-alpha (TNF-alpha) elevated at the beginning of the hypothermia, whereas serum levels of interleukin (IL)-1beta and interferon (IFN)-gamma remained unchanged. A nonselective cyclooxygenase inhibitor (indomethacin, 5 mg/kg, s.c.) inhibited hypothermia and serum TNF-alpha elevation, which resulted in an acceleration of the subsequent pyrogenic response. Moreover, a nonselective inhibitor of nitric oxide synthase (nitro L-arginine methyl ester (L-NAME), 10 mg/kg, s.c.) not only abolished fever but also prolonged the initial hypothermic response. These data suggest that the hypothermic component of low dose LPS-induced dual response is a regulated decrease in Tb. The data also suggest that hypothermia and fever may occur independently as two different thermoregulatory strategies against immune challenge in rats.
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PMID:Characterization of the hypothermic component of LPS-induced dual thermoregulatory response in rats. 1190 Jul 81


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