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

Nitric oxide (NO) is known to be involved in the neuropathological mechanisms triggered by excitatory aminoacids. NO(+) neurons in the brain may be detected histochemically by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical technique, as the latter readily labels NO synthase in the central nervous system (CNS). NADPH-d stained striatal and cortical sections were studied in 6-month-old male Sprague-Dawley rats exposed to perinatal asphyxia (PA) at 37 degrees C, as well as in animals subjected to PA plus hypothermia treatment at 15 degrees C. Quantitative image analysis was performed to compare the staining pattern in the various groups. NADPH-d(+) neurons in striatum and cortex from subsevere and severe asphyctic animals showed a significant increase in soma size and in dendritic processes versus controls and hypothermia-treated rats. These findings indicate that chronic NO changes are involved in postischemic striatal and cortical alterations induced by PA that may be prevented by hypothermia.
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PMID:Long term changes in NADPH-diaphorase reactivity in striatal and cortical neurons following experimental perinatal asphyxia: neuroprotective effects of hypothermia. 913 44

The exact mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is not fully understood. The present study was conducted to investigate the effects of mild hypothermia on trauma-induced synthesis of nitric oxide (NO), which has been implicated in the pathogenesis of ischemic brain damage associated with glutamate neurotoxicity. Cerebral contusion was created in the rat parietal cortex by a weight-drop method, and extracellular concentrations of the NO end products nitrite and nitrate were measured using in vivo brain microdialysis and capillary electrophoresis under normothermic (37 degrees C) and mild hypothermic (32 degrees C) conditions. In normothermic animals, the level of NO end products increased markedly 10 min after contusion, reaching a maximum level at 20 min. In the hypothermic rats, such increases were absent. Although it is unknown whether endothelial NO synthase, neuronal NO synthase, or both caused the elevation of the NO end products seen in the normothermic animals, the present results indicate that inhibition of NO synthesis may play a part in hypothermic cerebroprotection following TBI.
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PMID:Effects of mild hypothermia on nitric oxide synthesis following contusion trauma in the rat. 919

In order to elucidate the mechanism(s) of neuronal protection by hypothermia against ischemic damage, we examined the effect of lowering temperature on the microglial activation that is thought to cause the development of ischemia-induced neuronal damages. Cultured microglia from neonatal rats were measured for microglial activation by the following indices: production of superoxide and nitric oxide by the methods of acetyl-cytochrome c reduction and nitrite accumulation in the culture medium, respectively, and cell proliferation evaluated by [3H]thymidine uptake. At 30 degrees C, superoxide production induced by phorbol ester was approximately as low as 30% of the control at 37 degrees C, and nitric oxide production after addition of lipopolysaccharide was decreased to approximately 25% of the control. The time course of nitric oxide production indicates that the induction of nitric oxide synthase seemed to be significantly suppressed by lowering temperature. In addition, the proliferation of microglia was remarkably inhibited at 30 degrees C. The level of proliferation in the hypothermic condition is much lower in microglia (14% of the control) than those in astrocytes cultured from brain cortices (96%) and fibroblasts cultured from brain meninges (53%), suggesting that the microglial activation is highly susceptible to lowering temperature. The present study indicates that hypothermia potently inhibits proliferation, superoxide and nitric oxide production of cultured microglia and that the hypothermic protection against postischemic neuronal damage might be, at least in part, due to the suppression of microglial activation.
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PMID:Hypothermic suppression of microglial activation in culture: inhibition of cell proliferation and production of nitric oxide and superoxide. 930 Apr 14

Hypothermia is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, the NO pathway has been suggested to be involved in thermoregulation. In the present study, we assessed the participation of nitric oxide in hypoxia-induced hypothermia by means of NO synthase inhibition using NG-nitro-L-arginine methyl ester (L-NAME). The rectal temperature of awake, unrestrained rats was measured before and after hypoxia or L-NAME injection or both treatments together. Control animals received saline injections of the same volume. We observed a significant (P < 0.05) reduction in body temperature of 1.32 +/- 0.36 degrees C after hypoxia (7% inspired O2) and of 0.96 +/- 0.42 degree C after L-NAME (30 mg/kg body wt) injected intravenously. When the two treatments were combined, no significant difference in body temperature was observed. To assess the role of central thermo-regulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle or intravenously. Intracerebroventricular injection of L-NAME caused an increase in body temperature, but when L-NAME was combined with hypoxia (7% inspired O2) no change in body temperature was observed. Intravenous injection of 1 mg/kg L-NAME had no effect. The data indicate that NO plays a major role in hypoxia-induced hypothermia at central rather than peripheral sites.
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PMID:Role of the nitric oxide pathway in hypoxia-induced hypothermia of rats. 932 75

Perinatal asphyxia (PA) produces changes in nitric oxide synthase (NOS) activity in neuronal and endothelial cells of the striatum and neocortex. The changes were examined using a histochemical NADPH-diaphorase (NADPH-d) staining method. Newborn rats were exposed to severe PA at 37 degrees C and other groups were subjected to severe PA under hypothermic condition (15 degrees C) for 20 or 100 min, respectively. Quantitative image analysis was performed on the striatum and neocortex in order to count cell number of reactive neurons and to compare the pattern of staining between the different groups of animals. Severe asphyctic pups showed an important neuronal loss in striatum and neocortex that was reduced by hypothermia. NADPH-d(+) neurons with reactive processes were found in the lateral zone of the striatum and neocortex in asphyctic pups. Controls and hypothermic striatum showed rounded cells without reactive process, while no cells were stained in cortex. There was also an increase in NADPH-d activity in endothelial cells in severe asphyctic pups in striatum and neocortex vs control and hypothermically treated animals. Our data evidenced that an inappropriate activation of NOS in neuronal and endothelial cells induced by PA is related to neuronal injury. Hypothermia inhibits neuronal injury and may be a valuable neuroprotective agent.
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PMID:Short-term changes in NADPH-diaphorase reactivity in rat brain following perinatal asphyxia. Neuroprotective effects of cold treatment. 933 71

Striatal and cortical neurons containing nitric oxide synthase (NOS) were studied in adult rats subjected to different periods of perinatal asphyxia (PA) using immunohistochemistry at both light microscopy (LM) and electron microscopy (EM). Another group was subjected to PA + hypothermia to study its neuroprotective effect. Quantitative image analysis was performed on the striatum and neocortex in order to count the number of immunoreactive neurons and to compare the pattern of staining between the different groups. Six-month-old rats that suffered subsevere and severe PA demonstrated, at LM, cytomegaly of the striatal and neocortical neurons containing NOS. Control and hypothermic neurons were more weakly immunostained than PA neurons. Subsevere and severe asphyctic rats showed an important neuronal loss that was reduced by hypothermic treatment. The PA group disclosed, at EM, dense electronic bodies distributed in terminals surrounding synaptic vesicles and in dendrites. Non-NOS-containing neurons showed signs of degeneration, such as dark cytoplasm and shrunken nuclei. Surrounding the blood vessels, we observed a clear edema. The immunolabeling in hypothermic rats resembled that observed in controls. These data suggest that subsevere and severe PA induces chronic changes in the neuronal content of NOS in the striatum and neocortex. Degeneration observed in neurons surrounding cytomegalic NOS-containing cells may be due to the excess of NO in their environment. Moreover, the chronic alterations produced by PA seem to be prevented by hypothermia.
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PMID:Ultrastructural changes in nitric oxide synthase immunoreactivity in the brain of rats subjected to perinatal asphyxia: neuroprotective effects of cold treatment. 943 23

The role of nitric oxide (NO) in the development of cannabinoid tolerance was examined by using N(omega)-nitro-L-arginine methyl ester (L-NAME) as an inhibitor of NO synthase. R(+)-[2,3-Dihydro-5-methyl-3 [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napht halenyl)methanone mesylate (WIN 55,212-2), a cannabinoid receptor agonist, or L-NAME plus WIN 55,212-2 was acutely or chronically injected i.p. to mice and analgesia, body temperature and immobility were measured. A single injection of WIN 55,212-2 induced time- and dose-dependent analgesia, hypothermia and catalepsy. L-NAME (50 mg/kg), which per se was ineffective, administered 20 min before WIN 55,212-2 did not modify the analgesic, hypothermic and cataleptic responses to the cannabinoid. When WIN 55,212-2 was administered once a day, the animals became completely tolerant to the analgesic, hypothermic and cataleptic effects within five, seven and nine days respectively. L-NAME injected once daily 20 min before WIN 55,212-2 inhibited the development of tolerance to the hypothermic and cataleptic actions but not to the analgesic action of WIN 55,212-2. Since L-NAME given chronically by itself did not modify the analgesia, hypothermia and catalepsy induced by acute administration of WIN 55,212-2, our findings suggest L-NAME acts with some selectivity on the mechanisms involved in cannabinoid tolerance.
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PMID:A role of nitric oxide in WIN 55,212-2 tolerance in mice. 957 Apr 63

The striatum is rich in nitric oxide synthase (NOS). It is present in a dense fiber network and in a few medium-sized non-spiny interneurons. Previous work showed chronic overexpression of NOS in the rat striatum after a severe perinatal asphyctic (SPA) insult. This was prevented by hypothermia. We investigated whether the overexpression of NOS was accompanied by increased NOS activity. As nitric oxide (NO) is a potent activator of the soluble isoform of guanylyl cyclase, we measured striatal 3',5'-cyclic monophosphate (cyclic GMP) synthesis in 10-day-old (P10) rat pups that were subjected to SPA during normothermia or hypothermia during or after the insult. Cyclic GMP levels in striatal tissue from control pups were approximately 25.8 pmol/mg protein and in the SPA group approximately 38.1 pmol/mg protein (p<0.01). Hypothermia, during as well as after insult, prevented this increase of cyclic GMP. Nomega-nitro-L-arginine (L-NAME) (0.1 mM) decreased cyclic GMP levels in control, SPA and hypothermia treated pups to similar low levels (approximately 8% of level without L-NAME). Sodium nitroprusside (SNP) stimulated cyclic GMP showed no differences between the four groups. This indicates that high cyclic GMP levels in the striatum of rats subjected to SPA are caused by increased NOS activity. Hypothermia after an asphyctic insult could be a promising treatment.
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PMID:Hypothermia during or after severe perinatal asphyxia prevents increase in cyclic GMP-related nitric oxide levels in the newborn rat striatum. 959 57

Lipopolysaccharide (LPS) and homologous cytokines were tested for their effect on core temperature in mice using battery-operated telemetric devices placed in the peritoneal cavity. One microgram LPS injected intraperitoneally (i.p.) induced a biphasic effect on core body temperature (Tc), a rapid decrease in Tc with a peak around 30-45 min followed by a prolonged rise around 150-300 min. When a higher dose of LPS (5 microg) was used, the hypothermia was increased in magnitude and lasted much longer, and no fever was observed. Both the decrease and the increase in Tc caused by LPS were prevented by pretreating the mice with indomethacin, a cyclooxygenase inhibitor, but not by a nitric oxide synthase inhibitor. Mouse interleukin-1beta (mIL-1beta, 100 ng, i.p.) induced changes resembling those to LPS, a short-lived decrease in Tc, followed by a small increase. When 1 microg mIL-1beta was injected a profound hypothermia lasting more than 3 h was observed. Mouse IL-6 (1 microg) failed to alter core temperature after either intravenous (i.v.) or i.p. administration. Human IL-6 was also ineffective. Recombinant mouse tumor necrosis factor-alpha (mTNFalpha) also failed to alter the core temperature of mice when injected at a dose of 1 microg (i.p. or i.v.). However, a higher dose of mTNFalpha (5 microg i.p.) caused a short-lived decrease in Tc, followed by a small increase. Similar results were obtained with LPS and the cytokines in C57Bl/6J mice, except that mIL-1beta was ineffective in this strain. These results indicate that the endocrine, neurochemical and behavioral responses to IL-1, IL-6 and TNFalpha administration cannot be explained by changes in Tc, although they may contribute to them. They also suggest that IL-1beta may account for the fever observed following LPS, but that these cytokines are probably not the only factors involved in LPS-induced changes in Tc.
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PMID:Effect of homologous interleukin-1, interleukin-6 and tumor necrosis factor-alpha on the core body temperature of mice. 965 Aug 15

This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxide (NO) synthase in post-ischemic retinal injury in rats. Cell loss in the ganglion cell layer and thinning of the inner plexiform layer were observed 7 days after ischemia. Cell loss in the ganglion cell layer but not thinning of the inner plexiform layer was reduced by hypothermia during ischemia. Intravenous injection of dizocilpine (MK-801) or Nomega-nitro-L-arginine methyl ester (L-NAME) prior to ischemia ameliorated retinal injury. These results suggest that activation of NO synthase following NMDA receptor stimulation is involved in ischemia-induced retinal injury.
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PMID:Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina. 968 14


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