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

The cerebroprotective effects of mild hypothermia have been extensively studied in various animal models of ischemia, but the mechanism by which mild hypothermia diminishes ischemic injury is not well understood. Nitric oxide (NO) has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures, and its synthesis is acutely increased during focal ischemia in vivo. To evaluate possible mechanisms of hypothermic neuroprotection, we measured markers of NO synthesis--nitrite and cyclic guanosine monophosphate (cGMP) levels and NO synthase activity--during right middle cerebral artery occlusion (MCAO) in the rat under normothermic (36.5 degrees C) and mild hypothermic (33 degrees C) conditions. There was a significant increase in nitrite concentration in the right hemisphere versus the left under normothermic conditions at 10 and 20 minutes after MCAO (P < 0.01), with a return to baseline levels by 60 minutes. The increase in cortical nitrite levels in the right hemisphere versus the left was not observed with mild hypothermia. There was a threefold increase in cGMP synthesis in the normothermic right cortex 10 minutes after MCAO (P < 0.05). This rise in cGMP did not occur in hypothermic animals, and the right to left cortical disparity in cGMP production was abolished. Finally, the significant increase in NO synthase activity seen in the normothermic ischemic cortex was absent in hypothermic rats (P < 0.05). These results suggest that mild hypothermia (33 degrees C) modulates the burst of nitric oxide synthesis during cerebral ischemia and may account, at least partially, for its cerebroprotective effects.
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PMID:Effect of mild hypothermia on nitric oxide synthesis during focal cerebral ischemia. 752 62

High doses of 3,4-methylenedioxymethamphetamine (MDMA) have been shown to cause long-lasting depletions of central serotonin (5-HT) which are indicative of neuronal toxicity. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (DZ) attenuates depletions of 5-HT induced by MDMA. Because DZ has been shown to induce hypothermia in rat models of ischemia, the purpose of this study was to assess whether DZ and two other glutamate antagonists, CGS 19755 (CGS) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), protect against MDMA-induced 5-HT depletions by induction of hypothermia. Male Sprague-Dawley rats were injected with either saline (SAL), DZ (2.5 mg/kg), CGS (25.0 or 50.0 mg/kg x 2 injections) or NBQX (30.0 mg/kg x 2 injections or 55.0 mg/kg x 3 injections) followed by either MDMA (40.0 mg/kg) or SAL. Core body temperature (TEMP) was monitored for 4 h or longer using radiotelemetry. Base-line TEMP was between 37.0 and 37.6 degrees C. Administration of DZ with MDMA decreased TEMP to 34.0 +/- 0.39 degrees C within 2 h of the MDMA injection, and also protected against serotonergic toxicity. Neither SAL/MDMA nor DZ/SAL had an effect on TEMP over the same period. When rats were treated with DZ/MDMA and TEMP was maintained between 38.4 degrees C and 40.4 degrees C for 4 h, protection against 5-HT depletion was abolished. Coadministration of the competitive NMDA antagonist CGS with MDMA-resulted in a decrease in TEMP to 34.5 +/- 0.27 degrees C, and provided partial protection against 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of hypothermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 and NBQX. 753 65

Posttraumatic hypothermia reduces the extent of neuronal damage in remote cortical and subcortical structures following traumatic brain injury (TBI). We evaluated whether excessive extracellular release of glutamate and generation of hydroxyl radicals are associated with remote traumatic injury, and whether posttraumatic hypothermia modulates these processes. Lateral fluid percussion was used to induce TBI in rats. The salicylate-trapping method was used in conjunction with microdialysis and HPLC to detect hydroxyl radicals by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular glutamate was measured from the same samples. Following trauma, brain temperature was maintained for 3 h at either 37 or 30 degrees C. Sham-trauma animals were treated in an identical manner. In the normothermic group, TBI induced significant elevations in 2,3-DHBA (3.3-fold, p < 0.01), 2,5-DHBA (2.5-fold, p < 0.01), and glutamate (2.8-fold, p < 0.01) compared with controls. The levels of 2,3-DHBA and glutamate remained high for approximately 1 h after trauma, whereas levels of 2,5-DHBA remained high for the entire sampling period (4 h). Linear regression analysis revealed a significant positive correlation between integrated 2,3-DHBA and glutamate concentrations (p < 0.05). Posttraumatic hypothermia resulted in suppression of both 2,3- and 2,5-DHBA elevations and glutamate release. The present data indicate that TBI is followed by prompt increases in both glutamate release and hydroxyl radical production from cortical regions adjacent to the impact site. The magnitude of glutamate release is correlated with the extent of the hydroxyl radical adduct, raising the possibility that the two responses are associated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. 756 68

Profound hypothermia induced with cardiopulmonary bypass has a protective effect on spinal cord function during operations on the thoracoabdominal aorta. The mechanism of this protection remains unknown. It has been proposed that the release of excitatory amino acids in the extracellular space plays a causal role in irreversible neuronal damage. We investigated the changes in extracellular neurotransmitter amino acid concentrations with the use of in vivo microdialysis in a swine model of spinal cord ischemia. All animals underwent left thoracotomy and right atrium-femoral artery cardiopulmonary bypass with additional aortic arch perfusion. Lumbar laminectomies were then done and microdialysis probes were inserted stereotactically in the anterior horn of the second and fourth segments of the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min and 15-minute samples were assayed by high-performance liquid chromatography. Group 1 animals (n = 6) underwent aortic clamping distal to the left subclavian artery and proximal to the renal arteries for 60 minutes at normothermia (37 degrees C) and group 2 animals (n = 5) were cooled to a rectal temperature of 20 degrees C before application of aortic clamps, maintained at this level during cardiopulmonary bypass until the aorta was unclamped, and then slowly rewarmed to 37 degrees C. Seven amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and five putative inhibitory neurotransmitters (glycine, gamma-aminobutyric acid, serine, adenosine, and taurine). Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. The increase in aspartate concentration was not significant. The extracellular concentrations of glycine and gamma-aminobutyric acid also increased significantly during ischemia and reperfusion. Hypothermia uniformly prevented the release of amino acids in the extracellular space. Glutamate levels remained significantly decreased even after rewarming to normothermia whereas glycine levels returned to baseline values. These results are consistent with a role for excitatory amino acids in the production of ischemic spinal cord injury and suggest that the mechanism of hypothermic protection may be related to decreased release of these amino acids in the ischemic spinal cord.
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PMID:Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia. 1004 38

To define the part played by mild-to-moderate hypothermia in neuroprotection, it is necessary to take into account the thermoregulatory responses that occur in the normal human as the change in central temperature exceeds 0.2 degrees C. The mechanisms induced by cold are cutaneous vasoconstriction and shivering. They must be suppressed before starting controlled hypothermia. In these conditions, controlled moderate hypothermia between 32 and 35 degrees C does not seem to have deleterious side-effects, especially on coagulation. Caution is needed with the analysis of the numerous papers reporting experiments concerning the effects of moderate hypothermia in animals with induced cerebral ischaemia because of significant differences in the study designs. These differences concern mainly the time of onset of hypothermia, viz before or after ischaemia, the fact that the ischaemia is either global or focal, that it is caused by vascular occlusion posttraumatic or initiated by hypo or hyperglycemia. Some differences are also existing in the criteria used to appreciate the neuronal damage, as well as in the level of temperature and the site where it is measured. The mechanism of neuroprotection from moderate hypothermia seems to be not only a decrease in cerebral metabolism, but also involves a specific action on some intra-cellular events such as the blocking of the release of glutamate and of lipid peroxydation in brain tissue. An indirect proof of the neuroprotective effect of moderate hypothermia is the increase in the neuronal damage induced by moderate hyperthermia. It is conceivable that moderate hypothermia could exert a better neuroprotective effect than the drugs having this reputation, such as barbiturates, isoflurane and propofol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mild hypothermia and cerebral protection]. 767 76

Aspartate and glutamate each have been shown to improve cardiac recovery after hypoxia or ischemia under normothermic conditions, but whether their effects are additive and to what extent they are modified by hypothermia has not been studied systematically. We set out to compare the individual and combined protective effects of aspartate and glutamate during cardioplegic arrest under normothermic and hypothermic conditions in the rat. Using isolated working rat hearts, functional and metabolic recovery was assessed after 0.5 hours of potassium arrest at 37 degrees C or 5 hours at 2 degrees C in control hearts (C) and in hearts in which 20 mmol/L glutamate (G), 20 mmol/L aspartate (A), or both (A + G) was added to the cardioplegic solution. Under normothermic conditions, percentage recovery of prearrest work (mean +/- standard error of the mean) was as follows: C = 31.7 +/- 2.8, G = 34.8 +/- 0.2, A = 49.6 +/- 2.8*, A + G = 53.7 +/- 2.3*. Under hypothermic conditions, the values were as follows: C = 40.4 +/- 4.0, G = 45.2 +/- 2.3, A = 59.4 +/- 1.8*, A + G = 54.1 +/- 1.2* (*p < 0.01 versus C and G). Recovery of postischemic high-energy phosphate content followed the same pattern: A = A + G > G or C. Measurement of postischemic myocardial content of amino acids showed that recovery of function and energy status correlated with maintenance of myocardial levels of aspartate (r = 0.9; p < 0.01) but not glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differing protection with aspartate and glutamate cardioplegia in the isolated rat heart. 777 37

The cerebroprotective effects of hypothermia in focal models of ischemia are well established, but little is known about the underlying mechanisms of this form of brain protection. Cortical cooling in global transient ischemic models suggests that hypothermia limits glutamate excitotoxicity by decreasing the release of glutamate during ischemia. Few studies have examined glutamate release in the more physiological model of permanent focal ischemia. In this study, we used a rat model of middle cerebral artery occlusion (MCAO) of permanent focal ischemia. Extracellular glutamate concentration was analyzed bilaterally by microdialysis for 30 minutes before MCAO to 120 minutes after MCAO. Normothermic animals (n = 13) had a baseline glutamate concentration of 9.23 +/- 2.5 mumol/ml (mean +/- standard error of the mean) before MCAO. Extracellular glutamate rose quickly after vessel occlusion and peaked at 33.95 +/- 6.3 mumol/ml 30 minutes after MCAO. By 60 minutes after MCAO, this level had decreased to 25.14 +/- 6.3 mumol/ml; glutamate levels decreased slightly to 21.35 +/- 6.8 mumol/ml by 120 minutes. Hypothermic animals (n = 11) had an initial extracellular glutamate concentration of 5.22 +/- 1.3 mumol/ml before MCAO. This value rose gradually to a maximum of 10.69 +/- 3.3 microns/ml at 50 minutes after MCAO and then returned to a baseline value of 2.58 +/- 1.2 mumol/ml by 120 minutes. Contralateral control glutamate dialysates in the normothermic and hypothermic groups remained near baseline throughout the experimental period. The mean percentages of right hemispheric volumes occupied by infarcts were 11.96 +/- 1.68% in the hypothermic group and 19.77 +/- 2.03% in the normothermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraischemic hypothermia decreases the release of glutamate in the cores of permanent focal cerebral infarcts. 779 93

This review describes recently recognized pathophysiologic mechanisms responsible for brain damage during ischemia and reperfusion and new therapeutic concepts developed on a rational basis. Mediators of secondary damage include excitotoxins such as glutamate, acidosis, free radicals, and the disturbance of the microcirculation seen in the early phase of recirculation. Glutamate is an excitatory neurotransmitter, which may turn neurotoxic when the energy supply is limited. Tissue acidosis down to pH 6.0 develops regularly in cerebral ischemia and disturbs a variety of neuronal functions, causing glial swelling and neuronal death. Free radicals attack brain lipids, the cell membrane and myelin in particular, and are produced during reperfusion. Disturbance of the microcirculation aggravates ischemic damage. Suggested therapeutic approaches include glutamate antagonists, normalization of tissue acidosis, and use of new diuretics to reduce glial swelling, protection of the brain by free radical scavengers such as 21-aminosteroids, tocopherol, allopurinol or superoxide dismutase, and hypothermia. Ways of ensuring fast reperfusion, including hypervolemic hemodilution and blood pressure stabilization, are suggested for resuscitation or early stroke. All data available indicate that the combination of several successful therapeutic principles will significantly improve outcome.
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PMID:[Neuroprotection. Models and basic principles]. 784 Apr 11

To elucidate the precise mechanism of neuronal protection by brain hypothermia, we conducted an investigation as to what effect low temperature had on glutamate-induced intracellular free calcium ([Ca2+]i) accumulation and cell death in cultured hippocampal neurons. Fifteen minutes of exposure to either 100 microM or 1 mM glutamate uniformly induced a marked increase in [Ca2+]i, with delayed recovery and massive neuronal death under the conditions of both 37 degrees C and 30 degrees C. The study indicated that brain hypothermia cannot save neurons once glutamate is released during ischemia, and that intraischemic hypothermia in vivo probably prevents the development of ischemic neuronal injury by suppressing extracellular glutamate release.
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PMID:Effect of low temperature on glutamate-induced intracellular calcium accumulation and cell death in cultured hippocampal neurons. 790 21

Moderate hypothermia has been shown to have therapeutic utility in the treatment of cerebral ischemia and to attenuate the rise in interstitial concentrations of the excitatory amino acid neurotransmitter L-glutamate. In this study, the influence of hypothermia on traumatic brain injury (TBI) was assessed using a controlled cortical impact model. Rats were cooled to 32.0-33.0 degrees C at least 30 min before injury and maintained at this temperature for 2 h after injury. The influence of hypothermia on the immediate increase in interstitial concentrations of aspartate and glutamate and the volume of the resultant lesion 14 days after TBI was then determined. The volume of the lesion (mean +/- SEM) in hypothermic animals (8.2 +/- 1.3 mm3, n = 9) was significantly smaller than that of normothermic animals (13.2 +/- 1.7 mm3, n = 8). By contrast, TBI-induced increases in dialysate concentrations of aspartate and glutamate were similar at the two temperatures. Thus, aspartate content (nmol/10 min) in animals maintained at 37.0-37.5 degrees C (n = 6) and 32.0-33.0 degrees C (n = 6) increased from respective mean preinjury values of 0.05 +/- 0.02 and 0.08 +/- 0.02 to much larger peak values (0.78 +/- 0.13 and 0.71 +/- 0.09, respectively). Similarly, under normothermic conditions glutamate content (nmol/10 min) increased from 0.13 +/- 0.03 to 3.08 +/- 0.52 and from 0.19 +/- 0.06 to a peak value of 3.09 +/- 0.26 under hypothermic conditions. These data clearly demonstrate the cytoprotective action of moderate hypothermia and further suggest that this action is not mediated by attenuation of the rise in interstitial concentrations of aspartate and glutamate.
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PMID:Therapeutic hypothermia is cytoprotective without attenuating the traumatic brain injury-induced elevations in interstitial concentrations of aspartate and glutamate. 790 37


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