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

Hypothermia was first applied therapeutically as a local anesthetic and later was used to achieve organ protection during procedures necessitating circulatory interruption. Profound whole-body hypothermia, typically carried out in conjunction with extracorporeal bypass, has long been employed during cardiac and neurosurgical operative procedures. More recently, studies in small-animal experimental models of cerebral ischemia have provided persuasive evidence that even small decreases in brain temperature confer striking protection against ischemic neuronal injury. By contrast, small elevations of brain temperature during ischemia accelerate and extend pathologic changes in the brain and promote early disruption of the blood-brain barrier. Hypothermia retards the rate of high-energy phosphate depletion during ischemia and promotes postischemic metabolic recovery. More importantly, mild intraischemic hypothermia markedly attenuates the release of glutamate into the brain's extracellular space and significantly diminishes the release of dopamine. Similarly, the inhibition of calcium-calmodulin-dependent protein kinase II triggered by normothermic ischemia is prevented by hypothermia, as is the ischemia-induced translocation and inhibition of the key regulatory enzyme protein kinase C. Hypothermia also appears to facilitate the resynthesis of ubiquitin following ischemia. Studies of potential clinical importance have shown that moderate hypothermia is capable of attenuating ischemic damage even if instituted early in the postischemic period. In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the infarct size (particularly in the setting of reversible middle cerebral artery occlusion); conversely, hyperthermia markedly increases the infarct volume. These studies underscore the importance of monitoring and regulating the brain temperature during experimental studies of cerebral ischemia to insure a consistent pathologic outcome and to avoid the false attribution of "pharmacoprotection" to drugs that reduce the body temperature. The measurement of brain temperature is now practicable in neurosurgical patients requiring invasive monitoring, and human studies have shown that cortical and cerebroventricular temperatures may exceed systemic temperatures. Mild to moderate decreases in brain temperature are neuroprotective in cerebral ischemia, while mild elevations of brain temperature are markedly deleterious in the setting of ischemia or injury. It is anticipated that controlled clinical trials of therapeutic brain temperature modulation will be undertaken over the next several years.
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PMID:Therapeutic modulation of brain temperature: relevance to ischemic brain injury. 138 56

To examine the expression of heat shock protein (hsp) in each organ on autopsy in 11 deaths from hypothermia, we performed immunological staining of specimens from each organ using an antibody to hsp, ubiquitin (Ub). Staining of the liver, kidneys, lungs and pancreas revealed a high level of Ub expression in the cytoplasm and nuclei. However, staining of the same specimens of all controls revealed no Ub expression in the cytoplasm or nuclei. This finding suggests that cells are affected by stress even at a low temperature, and may be important in clarifying the cellular kinetics in death from hypothermia.
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PMID:Expression of ubiquitin protein in each organ at death from hypothermia. 915 83

Protein synthesis is severely depressed in hibernating mammals. In the absence of significant protein synthesis, the continued turnover of proteins as a function of normal cellular activity would result in the net depletion of protein pools. We measured levels of ubiquitylated proteins in the gut of thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) and liver of golden-mantled ground squirrels ( Spermophilus lateralis). In both tissues, ubiquitin conjugate concentrations increased during entrance into torpor and were elevated 2-3 fold by late torpor compared with levels in active animals. The data are consistent with a depression of proteolysis with a resultant high level of ubiquitylated proteins during the natural hypothermia of torpor. The periodic returns to euthermy during the hibernation season allow for degradation of these conjugated proteins and may serve to restore protein pools.
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PMID:Ubiquitin conjugate dynamics in the gut and liver of hibernating ground squirrels. 1191 8

Hibernation torpor provides an excellent natural model of tolerance to profound reductions in blood flow to the brain and other organs. Here, we report that during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the brain, liver, and kidney. The level of small ubiquitin-related modifier (SUMO) conjugation coincides with the expression level of Ubc9, the SUMO specific E2-conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as markedly as hibernation torpor. Increased SUMO conjugation (induced by Ubc9 overexpression, ischemic preconditioning (PC)+/-hypothermia) was necessary and sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/glucose deprivation (OGD) ('in vitro ischemia'); decreased SUMO conjugation (induced by a dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These data indicate that post-translational modification of proteins by SUMOylation is a prominent feature of hibernation torpor and is critical for cytoprotection by ischemic PC+/-hypothermia in SHSY5Y cells subjected to OGD.
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PMID:Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells. 1695 77

Dysfunction of the ubiquitin-proteasome system has recently been linked to stroke. Ischemia may cause increased protein misfolding and inhibit the proteasome, shifting the balance from free ubiquitin to conjugated ubiquitin. In this study, we examine the effect of hypothermia on the distribution of total and free ubiquitin, as well as the levels of conjugated ubiquitin after experimental stroke using a focal cerebral ischemia model. We show that hypothermia prevents redistribution of ubiquitin following ischemia, largely through preservation of intracellular cytoplasmic free ubiquitin. We also show that hypothermia blocks the increase in conjugated ubiquitin observed after stroke. Our data indicate that hypothermia's neuroprotection is mediated, in part, through preservation of ubiquitin-proteasome system function.
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PMID:Hypothermia blocks ischemic changes in ubiquitin distribution and levels following stroke. 1704 55

We examined the immunohistochemical distributions of ubiquitin (Ub) and myoglobin (Mb) in human kidney tissues to assist the pathological assessment of death due to trauma. Medicolegal autopsy cases at our institute (n=138: 0-96 years of age, 105 males and 33 females) were examined. Causes of death were blunt injury (n=31), sharp injury (n=15), poisoning (n=11), drowning (n=10), fire fatalities (n=25), hypothermia (n=7), asphyxiation (n=14), hyperthermia (n=3), and natural diseases (n=22) for controls. Immunostaining of Ub and Mb was performed on the formalin-fixed paraffin-embedded kidney tissue sections. Quantitative analyses by estimating the proportion of Ub- and Mb-positive cells (%positivity) of renal tubule epithelial cells showed that the positivities for Ub and Mb were higher in subjects who died due to fire, blunt injury, sharp injury and fatal hypothermia than in other groups. The Ub-positivity correlated with the severity of airway thermal injury in fire deaths, survival time in blunt injury, and serum markers for renal failure in deaths due to sharp injury. Concomitant increases in the tubular Mb- and Ub-positivities were characteristic to deaths from injury and hypothermia. These findings suggest that Ub may serve as a sensitive indicator of the fatal influence of traumas.
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PMID:Immunohistochemical investigation of ubiquitin and myoglobin in the kidney in medicolegal autopsy cases. 1716 80

Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.
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PMID:Hypothermia blocks beta-catenin degradation after focal ischemia in rats. 1824 48

Various cardiovascular operations are performed during conditions of deep hypothermic circulatory arrest. Here we investigated the effects of deep hypothermia on the small ubiquitin-like modifier (SUMO) conjugation pathway using a clinically relevant animal model of deep hypothermic cardiopulmonary bypass (DHCPB). Deep hypothermic cardiopulmonary bypass induced a marked activation of the SUMO conjugation pathway and triggered a nuclear translocation of SUMO2/3-conjugated proteins. Furthermore, DHCBP significantly modified gene expression. Activation of the SUMO conjugation pathway is believed to protect neurons from damage caused by low blood flow. This pathway may, therefore, play a key role in defining the outcome of cells exposed to DHCPB.
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PMID:Deep hypothermia markedly activates the small ubiquitin-like modifier conjugation pathway; implications for the fate of cells exposed to transient deep hypothermic cardiopulmonary bypass. 1924 Jul 42

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.
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PMID:Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia. 1955 86

A 14-year-old female alpaca (Vicugna pacos) was presented with a 1-week history of lethargy and anorexia and a 2-day history of recumbency, trembling, and hypothermia. There were no significant gross findings on postmortem examination. Hematoxylin and eosin-stained sections of brain demonstrated the presence of intracytoplasmic crystalline eosinophilic rod-shaped inclusions, mainly in the hippocampal pyramidal cells. Immunohistochemical staining for synuclein, tau protein, ubiquitin, and smooth muscle actin was negative. All inclusions were positive with phosphotungstic acid hematoxylin. Ultrastructurally, the inclusions were multilamellar and filamentous with longitudinal herringbone pattern and cross-sectional latticelike structure. The combination of hematoxylin and eosin appearance, special stains, immunostaining, and ultrastructural findings was consistent with Hirano-like bodies. The Hirano-like bodies were highly unlikely to be the cause of the neurologic signs experienced by this alpaca. To the authors' knowledge, this is the first report of spontaneous cerebral Hirano-like bodies in an alpaca.
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PMID:Cerebral Hirano-like bodies in an alpaca (Vicugna pacos): histologic and ultrastructural characterization. 2155 25


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