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

Isolated embryonic retinas were metabolically stressed by inhibition of glycolysis either with iodoacetate (IOA) or by glucose withdrawal plus 10 mM 2-deoxy-D-glucose, and the effects of hypothermia were examined. Incubation at 30 versus 37 degrees C during 30 min of hypoglycemia with IOA completely reduced the rapid swelling-related GABA release [6 +/- 2 vs. 68 +/- 10 nmol/100 mg of protein (mean +/- SEM) for 30 and 37 degrees C, respectively]. Histology of the retina immediately following 30 min of metabolic stress at 30 degrees C appeared normal, whereas that at 37 degrees C showed a pattern of acute edema, characteristic of NMDA-mediated acute excitotoxicity. Coincubation with a competitive or noncompetitive NMDA antagonist, respectively, CGS-19755 (10 microM) or MK-801 (1 microM), during 30 min of hypoglycemia at 37 degrees C completely prevented tissue swelling, whereas extracellular GABA content remained at basal levels, indicating that the cytotoxic effects of IOA treatment for 30 min at 37 degrees C were NMDA receptor mediated. Longer periods of hypoglycemia at 37 degrees C produced acute toxicity that was only partially NMDA receptor mediated. Hypothermia delayed the onset of NMDA-mediated toxicity by 30-60 min. At 30 degrees C, the rate of loss of ATP was slowed during the first several minutes of hypoglycemia (82 and 58% of maximal tissue levels at 30 and 37 degrees C, respectively, at 5 min, but by 10 min, ATP levels were comparably reduced. After a transient exposure of retina to 50 microM NMDA in Mg(2+)-free medium, hypothermia significantly attenuated acute GABA release by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothermia, metabolic stress, and NMDA-mediated excitotoxicity. 837 98

Hypothermia reduces ischemic brain damage, confounding interpretation of the neuroprotective effects of drugs. Specifically, the neuroprotectant MK-801 has been shown to cause hypothermia. Some have claimed that when body temperature is maintained, MK-801 is not a neuroprotectant, whereas others claim it retains its neuroprotective activity. MK-801 was evaluated for neuroprotective properties in free-regulating as well as temperature-maintained gerbils receiving 5 or 10 min of bilateral carotid occlusion. After 10 min of ischemia, free-regulating animals exhibited significant hypothermia (as low as 32 degrees C) and showed significant neuroprotection after 3 mg/kg IP MK-801. When a hyperthermic body temperature (38.5 degrees C) was maintained, no reduction in brain damage was evident after up to 10 mg/kg IP MK-801, even when occlusion time was reduced to 5 min. However, when a normothermic body temperature (36.5 degrees C) was maintained, 10 mg/kg IP MK-801 significantly reduced brain damage after 5 min of ischemia. Thus, although a higher dose of the drug is required, MK-801 can reduce ischemic brain damage in the absence of hypothermia. The need for this high dose suggests that mechanisms other than NMDA receptor complex antagonism may be involved in the neuroprotective actions of MK-801.
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PMID:Neuroprotection by MK-801 in temperature maintained gerbils. 853 64

While exposure of cultured spinal neurons to mild hypothermia provides some protection from physical trauma (dendrotomy), profound cooling (< 17 degrees C) causes unrelated neuronal injury and death, which can be prevented by treatment with NMDA receptor antagonists. To investigate the mechanism of hypothermic neuronal injury we examined the ultrastructure of cultured spinal neurons after 2 h of cooling to 17 degrees C or 10 degrees C, with or without the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate, and with or without rewarming to 37 degrees C. These groups were compared to cultures exposed to NMDA or to the calcium ionophore A23187. Patterns of ultrastructural change, involving cytoskeletal disruption, mitochondrial abnormalities and vacuolization of the cytoplasm, suggest a common mechanism of injury in all treatment groups, involving an elevation of intracellular calcium. Some neurons exposed to hypothermia, NMDA or ionophore developed beaded dendrites. Microtubules were fragmented in varicosities but not in the intervening constrictions; other organelles were largely excluded from the constrictions. Varicosities may form when organelles and cytoplasm accumulate as the result of disruption of transport and membrane stabilizing proteins by proteases activated by calcium influx via NMDA mediated channels. The periodic nature of the swellings may reflect inherently discontinuous distribution of molecular subunits of the cytoskeleton.
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PMID:Ultrastructural damage and neuritic beading in cold-stressed spinal neurons with comparisons to NMDA and A23187 toxicity. 854

The acute phase of spinal cord injury includes primary and secondary pathological patterns. Primary patterns include the effects of contusion, laceration, stretch of neural tissue and direct vascular trauma. These changes are irreversible. Secondary patterns include posttraumatic ischemic changes, loss of energy metabolism, oedema, release of cytotoxic substances such as free radicals, and electrolyte changes such as an increase in intracellular calcium ions. These changes may be reversible. This determines treatment strategies. Free-radical scavengers, opioid receptor antagonists include TRH and its analogues, calcium channel blockers, volume expander, osmotic diuretics, hypothermia, antioxidants, cycloxygenase inhibitors, serotonin antagonists and NMDA receptor antagonists were tested in experimental models during the last 4 years. The successful treatment should break the feedback loops and trails of secondary injury cascade in many places so combined treatment connected with many elements and surgery decompression is necessary.
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PMID:[The physiopathology of acute spinal cord injury and a hope for a successful treatment]. 865 40

A rapid and reproducible spinal motor neuron death occurs after sciatic nerve transection in neonatal rats. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, leukemia inhibitory factor and glial cell line-derived neurotrophic factor. Another hypothesis suggests that glutamate and its receptors has been implicated as possible mechanism for motor neuron death. In order to investigate the effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on axotomy-induced cell death in the spinal motor neurons of neonatal rats, we have studied neuroprotective effects of these receptor antagonists. Newborn rats were anesthetized with hypothermia. Sciatic nerve was transected near the obturator tendon in the left thigh. Animals were then treated daily with MK-801, APV, and CNQX for 14 days with intraperitoneal injections. Control animals received PBS in the same fashion. After the treatment, the number of spinal motor neurons in the L4-6 was counted. MK-801 and APV did not show any significant neuroprotective effect. By contrast, the number of surviving motor neurons was greater in animals that were treated with 1.0, 2.0 and 4.0 mg/kg of CNQX. This neuroprotective effect was not dose-related. We demonstrate that neuroprotective effect of CNQX on axotomized motor neurons, raises a possibility that such a agent may have therapeutic potential in motor neuronopathy and amyotrophic lateral sclerosis.
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PMID:CNQX prevents spinal motor neuron death following sciatic nerve transection in newborn rats. 874 38

Levine-prepared, female, Sprague-Dawley rats were used to investigate the possible protective effects of the NMDA receptor-blocker anesthetic ketamine and the Ca2+ channel-blocker verapamil (0.4 mg kg-1 'low dose', and 1.0 mg kg-1 'high dose') in rats during acute 2400 ppm carbon monoxide (CO) poisoning. Blood glucose and lactate concentrations, heart rate, mean arterial blood pressure (BP), body temperature (BT), neurological function and cerebral cortical water content were measured. In most cases glucose increased after 45 min and then fell to initial values after 90 min. Lactate concentration increased sharply during CO exposure in the saline and in the low- and high-dose verapamil groups, while the lactate increase in rats given ketamine at 40 mg kg-1 was significantly lower than with saline. Lactate was also significantly lower in these rats after 90 min than in the high-dose verapamil group. Lactate was normal in all four groups after 2 and 4 h of air recovery. Ketamine significantly lowered the heart rate prior to CO exposure, and the heart rate remained significantly below values for the saline and for the low- and high-dose verapamil groups throughout CO exposure. The BP decreased in all groups during CO exposure, and the BP recovery which took place in all four groups was significantly more rapid in the ketamine group. Recovery from CO-induced hypothermia was similar in the ketamine and saline groups, whereas rewarming tended to occur more slowly and less completely in the two verapamil-treated groups. There were no significant differences in neurological function among the four groups, as assessed after 4 h of recovery. However, cerebral edema was significantly reduced by treatment with 40 mg kg-1 ketamine as compared with saline. Verapamil at neither the low nor the high doses was of significant benefit in this regard. No rat in the 40 mg kg-1 ketamine group died during CO exposure, whereas all deaths in the other groups took place during CO exposure. The use of higher and lower doses of ketamine suggest 40-80 mg kg-1 as most effective in suppressing lactate production; 40 mg kg-1 ketamine may be optimal with regard to survival. The results suggest that ketamine is beneficial, when administered before and during acute severe CO poisoning, in reducing blood lactate and cerebral edema and in improving BP recovery and survival. Verapamil, in contrast, appears to provide no benefits in these respects.
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PMID:NMDA receptor-blocker ketamine protects during acute carbon monoxide poisoning, while calcium channel-blocker verapamil does not. 885 15

The purpose of this study was to develop a primate model for assessing EEG, behavior and histology, and to test the effect of NMDA receptor blockade in transient focal ischemia. Squirrel monkeys (Saimiri sciureus) under halothane anesthesia were subjected to 110 min of transient focal ischemia (n = 15) by temporary clip occlusion of the MCA. An eight-lead EEG was recorded. Neurobehavioral testing was done in a subgroup of animals (n = 6). Brain temperature (37.5 degrees C) was monitored and controlled to avoid hypothermia or intergroup temperature differences, and blood pressure was regulated to 60 mmHg. The entire brain was subserially sectioned, and 52 standardized coronal sections encompassing the infarct were examined histologically 2 wk after the ischemia. Animals were randomized to receive either (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) 1 mg/kg of maleate salt or carrier solution, 20 min and again at 12 h after the onset of ischemia. Cingulate and retrosplenial cortex were examined for NMDA-antagonist-induced neuronal necrosis. No reduction, or trend toward reduction of neurobehavioral deficit was seen with MK-801. MCA occulsion reduced EEG power over the ischemic hemisphere. MK-801 appeared to cause brain activation, and globally increased power at several frequencies. MK-801 did not reduce infarction in either neocortex (p > 0.05) or striatum (p > 0.05). No selective neuronal necrosis was seen in the cingulate or retrosplenial cortex. We conclude that MK-801 given 20 min after the onset of transient ischemia offers no significant neuroprotective effect against either neurobehavioral deficit or ischemic infarction in this model of transient focal ischemia. Further experiments in unanesthetized animals are necessary to determine if MK-801-induced necrosis exists in the gyrencephalic brain, but the enhancement of primate brain electrical activity by MK-801 suggests that brain activation occurs in primates as it does in rodents.
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PMID:Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia. 897 96

Hypothermia has been reported to be beneficial in CNS physical injury and ischemia. We previously reported that posttraumatic cooling to 17 degrees C for 2 h increased survival of mouse spinal cord (SC) neurons subjected to physical injury (dendrite transection) but that cooling below 17 degrees C caused a lethal NMDA receptor-linked stress to both lesioned and uninjured neurons. The present study tested whether cooling below 17 degrees C increases extracellular levels of excitatory amino acids (EAA). SC cultures were placed at 10 degrees C or 37 degrees C. Glutamate (Glu) and aspartate (Asp) levels were higher in the medium of the cooled cultures after 0.5 h (23 +/- 4 nM/microgram vs. 4 +/- 1 nM/microgram and 4 +/- 1 nM/microgram vs. 1 +/- 0 nM/microgram, respectively). The concentration of each EAA then declined and reached a plateau at 2-4 h that was still significantly higher than control levels (p < 0.0001, two-factor ANOVA, three cultures per group). Other amino acids (glycine, asparagine, glutamine, serine) showed an opposite pattern, with higher levels in the 37 degrees C group. Both NMDA and non-NMDA antagonists prevented the lethal cold injury. Survival of SC neurons cooled at 10 degrees C for 2 h and rewarmed for 22 h was 58% +/- 25% in the control group, 94% +/- 5% in the CNQX-treated group, 97% +/- 5% in the DAPV-treated group, and 99% +/- 2% in the group treated with both antagonists [p < 0.0006, one factor ANOVA, five cultures (> 120 neurons) per group]. These results show that death of neurons cooled to 10 degrees C is caused by elevated extracellular Glu and Asp and requires activation of both the NMDA and non-NMDA receptor subtypes.
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PMID:The role of excitatory amino acids in hypothermic injury to mammalian spinal cord neurons. 900 66

The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia.
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PMID:Opposite effects of GABAA and NMDA receptor antagonists on ethanol-induced behavioral sleep in rats. 908 18

Low extracellular pH decreases the activity of the N-methyl-D-aspartate (NMDA) glutamate receptor, and may thus limit neuronal calcium overload during cerebral ischemia. During induced hypothermia, alkaline pH ("alphastat regulation") is often used to preserve cardiac and enzymatic function. The purpose of this study is to measure the functional activity of cerebral cortex NMDA receptors over the range of temperatures used in profound hypothermic cardiopulmonary bypass (20-37 degrees C). Extracellular pH was varied over a broad range relevant to both alphastat and pH stat acid-base management (7.0-7.8). Change in cytosolic free calcium evoked by 50 microM NMDA in brain slices was used as an index of NMDA receptor activity. Cortical slices (300 microns thick) were loaded with fura-2 Aspartate Methyl for study in a fluorometer. At 37 degrees C, a change in extracellular pH from 7.1 to 7.8 increased the NMDA-evoked change in cytosolic calcium in brain slices by a factor of 4 (p < 0.05). In contrast, at 20 degrees C there was minimal effect of changing extracellular pH from 7.1 to 7.8 (27% increase). We conclude that hypothermia results in decreased pH sensitivity of the NMDA receptor. The results predict that different strategies of pH management during induced hypothermia may have limited impact on NMDA receptor-mediated processes, such as neuronal calcium overload.
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PMID:Interactive effects of pH and temperature on N-methyl-D-aspartate receptor activity in rat cortical brain slices. 910 Jan 91


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