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

Prolonged (2-6 h) cooling of monolayer cultures of dissociated murine spinal cord at temperatures below 17 degrees C caused pronounced swelling of neuronal perikarya and dendrites. The numbers of swollen neurons in a culture increased as the temperature was reduced, and at 7 degrees C-10 degrees C all of the neurons were swollen. On rewarming the cultures to 37 degrees C, the majority of the swollen neurons died (up to 74% at 10 degrees C). Glial cells were not affected. Addition of the NMDA antagonists D-2-amino-5-phosphonovalerate (DAPV, 100 microM), ketamine (100 microM), and dibenzocyclohepteneimine (MK801, 10 microM) to spinal cord cultures before lowering the temperature to 10 degrees C minimized the dendrosomatic swelling and reduced neuronal mortality from 74% to 10%. These data show a surprising sensitivity of some neurons to nonfreezing low temperatures and suggest direct involvement of the NMDA receptor in hypothermia-related neuronal death.
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PMID:NMDA antagonists prevent hypothermic injury and death of mammalian spinal neurons. 198 14

Excitatory amino acids and their receptors have been postulated to be involved in mediating ischemic neuronal damage. We occluded the bilateral carotid arteries for 5 min in gerbils to examine the effect of FR115427, a novel N-methyl-D-aspartate (NMDA) antagonist, on ischemic neuronal damage. FR115427 prevented hippocampal CA1 cell damage at a dose of 10 mg/kg and reduced spontaneous locomotor hyperactivity in gerbils after the development of ischemia at a dose of 32 mg/kg. The effective doses of MK801 were 3.2 mg/kg for preventing hippocampal CA1 cell damage and 1 mg/kg for reducing spontaneous locomotor hyperactivity. Moreover, we monitored the changes in body temperature of ischemic gerbils for 24 hr. The body temperature of ischemic gerbils significantly increased 1 hr after reperfusion. The pretreatment with FR115427 or MK801 prevented the hyperthermia provoked 1 hr after reperfusion in ischemic gerbils. In addition, the hypothermia was developed in gerbils treated with MK801 24 hr after reperfusion. However, FR115427 did not show hypothermia at any time. These results indicate that FR115427 has a protective effect against ischemic hippocampal CA1 cell damage after systemic administration, and this protective effect appears to be due to anti-NMDA activity.
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PMID:Protective effect of FR115427 against ischemic hippocampal damage in gerbils. 802 20

Both clinical and laboratory studies are being undertaken to investigate the deleterious neurologic and developmental effects associated with cardiopulmonary bypass, hypothermia, and circulatory arrest in the neonate and infant. A prospective, randomized clinical study of 171 neonates and young infants compared circulatory arrest with low-flow bypass (50 mL.kg-1.min-1). Circulatory arrest was associated with a higher incidence of early postoperative seizures as well as greater release of creatine kinase-BB. There was a strong correlation between duration of circulatory arrest and seizures (p = 0.004). The late consequences of these findings will be known at the completion of developmental assessment of all patients at 1 and 4 years of age. Laboratory studies have used a miniature piglet model that closely replicates clinical circulatory arrest. High-energy phosphate stores determined by magnetic resonance spectroscopy were maintained in animals undergoing 1 hour of low-flow bypass but became undetectable after 32 minutes of a 1-hour period of circulatory arrest. However, they returned to baseline within 3 hours of reperfusion as did cerebral blood flow and metabolism determined by microsphere studies. Piglets undergoing 1 hour of circulatory arrest showed more rapid recovery of cerebral adenosine triphosphate content and intracellular pH when managed with the pH-stat strategy during hypothermic bypass than with the more alkaline alpha-stat strategy. Other laboratory studies have examined pharmacologic methods of reducing cerebral injury associated with circulatory arrest including aprotinin, anti-CD18, neuronal receptor antagonists (MK801, NBQX), and blockade of glutamate release with adenosine in a cerebroplegia solution. These studies have suggested a number of promising approaches to improving the technique of circulatory arrest.
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PMID:Review of current research at Boston Children's Hospital. 826 70

The present study examined the effects of Dizocilpine (MK-801; a noncompetitive N-methyl-D-aspartate receptor antagonist) on flash-evoked potentials recorded from both the visual cortex (VC) and superior colliculus (SC) of chronically implanted hooded rats. The potentials were recorded at 5, 20, and 35 min following i.p. injections of saline, and of 0.1, 0.3, and 1.0 mg/kg MK-801 on separate days. The amplitude of VC component P1 was unaltered following drug treatment. N1 was increased in amplitude by the 0.1-, 0.3-, and 1.0-mg/kg doses, while two other negative peaks in the VC emerged, beginning with the 0.1-mg/kg dose, to complicate the waveform. One negative peak developed between N1 and P2, while the other effectively split peak P2 (forming P2A and P2B). P2A was depressed at all doses, while P2B was depressed at 0.1 mg/kg but augmented at the 1.0-mg/kg dose. N2 was elevated by the 0.3- and 1.0-mg/kg doses, while P3 was increased in amplitude by all doses. N3 was transiently enhanced by the 0.3-mg/kg dose. SC amplitudes were less affected, with P3 and N4 reduced in amplitude by the 0.3- and 1.0-mg/ kg doses. The latencies of most components in both structures were decreased, often with all doses, but generally at the later recording times. A second experiment demonstrated significant MK-801-induced hyperthermia at all of the above doses, although a higher dose of 3.0 mg/kg MK-801 caused hypothermia. The reduction in component latencies may, therefore, result at least in part from a drug-induced hyperthermia. A third experiment demonstrated MK-801-induced changes in locomotor activity in rats in an open field. The effects were both dose and time dependent. The 0.3-mg/kg dose of MK-801 produced significant increases in the number of line crossings from 20-60 min in comparison to the saline condition. Increases in the number of line crossings with the 1.0-mg/kg dose peaked at 15 min, and then gradually declined. It is unlikely, however, that these changes in movement can account for the effects of MK-801 on evoked potentials. In conclusion, the results show that blockade of the ion channel associated with the NMDA receptor produces profound changes in the activity of the neural pathways that are reflected in the middle components of the flash-evoked potential recorded from the VC.
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PMID:Effects of dizocilpine (MK-801) on flash-evoked potentials, body temperature, and locomotor activity of hooded rats. 1008 Feb 51

Sulfhydryl-reducing agents, such as dithiothreitol, modulate glutamate N-methyl-D-aspartate (NMDA) receptors. Since these receptors are involved in thermoregulatory processes, we studied the effects of their positive modulation, through a dithiothreitol-induced reduction of the receptor redox site, on thermoregulation in rats maintained at an ambient temperature of 20-22 degrees C. Given intraperitoneally at the dose of 25 and 50 mg x kg(-1), dithiothreitol induced dose-dependent hypothermia. The prior administration of 0.5 mg x kg(-1) of (+/-)-dizocilpine maleate (MK801), a non-competitive glutamate NMDA receptor antagonist, blocked most of the dithiothreitol-induced hypothermia. MK801 given alone was followed by slight transient hyperthermia. This confirms the involvement of NMDA receptors in thermoregulation and suggests that they might be under redox modulation.
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PMID:NMDA receptors are involved in dithiothreitol-induced hypothermia. 1152 42

We evaluated the efficacy of cycloheximide, heat stress, NMDA receptor blockade (MK801/AP-5), oxygen--glucose deprivation, hypoxia, hypothermia and TNFalpha preconditioning to protect cortical neurons from in vitro ischemic insults that result in acute necrotic and delayed apoptotic neuronal death. Preconditioning treatments were performed 22--24 h before in vitro ischemia. In vitro ischemia was carried out in 96-well microtitre strip-plates by washing neuronal cultures with a balanced salt solution containing 25 mM 2-deoxy-D-glucose and incubating in an anaerobic chamber. Glutamate receptor blockers were present during in vitro ischemia to induce delayed neuronal death. Cycloheximide, heat stress, MK801 and oxygen--glucose deprivation preconditioning were neuroprotective in both acute and delayed in vitro ischemic neuronal death models. AP-5 preconditioning and a 12 h post-MK801 preconditioning interval protected neurons from acute ischemic neuronal death only. Hypoxia, TNFalpha and hypothermic preconditioning provided no neuronal protection in the in vitro ischemia models. This study has confirmed for the first time that several preconditioning treatments can protect neurons from in vitro ischemia induced acute necrotic and delayed apoptotic neuronal death. In addition, a unique feature of this study is the finding that preconditioning could be induced in near-pure primary cortical neuronal cultures, thus confirming that ischemic tolerance is an intrinsic property of neurons and provides a simplified culture system for identifying neuroprotective proteins.
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PMID:Evaluation of preconditioning treatments to protect near-pure cortical neuronal cultures from in vitro ischemia induced acute and delayed neuronal death. 1184 73

Excitotoxicity mediated by the N-methyl-D-aspartate receptor (NMDAR) is believed to be a primary mechanism of neuronal injury following stroke. Thus, many drugs and therapeutic peptides were developed to inhibit either the NMDAR at the cell surface or its downstream intracellular death-signaling cascades. Nevertheless, the majority of focal ischemia studies concerning NMDAR antagonism were performed using the intraluminal suture-induced middle cerebral arterial occlusion (MCAO) model, which produces a large cortical and subcortical infarct leading to hypothalamic damage and fever in experimental animals. Here, we investigated whether NMDAR antagonism by drugs and therapeutic peptides was neuroprotective in a mouse model of distal MCAO (dMCAO), which produces a small cortical infarct sparing the hypothalamus and other subcortical structures. For establishment of this model, mice were subjected to dMCAO under normothermic conditions or body-temperature manipulations, and in the former case, their brains were collected at 3-72 h post-ischemia to follow the infarct development. These mice developed cortical infarction 6 h post-ischemia, which matured by 24-48 h post-ischemia. Consistent with the hypothesis that the delayed infarction in this model can be alleviated by neuroprotective interventions, hypothermia strongly protected the mouse brain against cerebral infarction in this model. To evaluate the therapeutic efficacy of NMDAR antagonism in this model, we treated the mice with MK801, Tat-NR2B9c, and L-JNKI-1 at doses that were neuroprotective in the MCAO model, and 30 min later, they were subjected to 120 min of dMCAO either in the awake state or under anesthesia with normothermic controls. Nevertheless, NMDAR antagonism, despite exerting pharmacological effects on mouse behavior, repeatedly failed to show neuroprotection against cerebral infarction in this model. The lack of efficacy of these treatments is reminiscent of the recurrent failure of NMDAR antagonism in clinical trials. While our data do not exclude the possibility that these treatments could be effective at a different dose or treatment regimen, they emphasize the need to test drug efficacy in different stroke models before optimal doses and treatment regimens can be selected for clinical trials.
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PMID:Hypothermia but not NMDA receptor antagonism protects against stroke induced by distal middle cerebral arterial occlusion in mice. 3212 2