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

Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR-1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.
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PMID:Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo. 946 23

Protective effect of hypothermia against DNA fragmentation in hippocampal CA1 field after transient forebrain ischemia in gerbils was evaluated by changing the magnitude of hypothermia. Inhibition of DNA fragmentation was proportional to the magnitude of hypothermia. The result indicates that, in terms of susceptibility to ischemia, hippocampal CA1 neurons are sensitive to a relatively small decrement of temperature, with temperatures </=35 degreesC being critical for the prevention of apoptotic process following transient forebrain ischemia.
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PMID:Relationship between magnitude of hypothermia during ischemia and preventive effect against post-ischemic DNA fragmentation in the gerbil hippocampus. 962 69

Russian knapweed is a perennial weed found in many parts of the world, including southern California. Chronic ingestion of this plant by horses has been reported to cause equine nigropallidal encephalomalacia (ENE), which is associated with a movement disorder simulating Parkinson's disease (PD). Repin, a principal ingredient purified from Russian knapweed, is a sesquiterpene lactone containing an alpha-methylenebutyrolactone moiety and epoxides and is a highly reactive electrophile that can readily undergo conjugation with various biological nucleophiles, such as proteins, DNA, and glutathione (GSH). We show in this study that repin is highly toxic to C57BL/6J mice and Sprague-Dawley rats and acutely induces uncoordinated locomotion associated with postural tremors, hypothermia, and inability to respond to sonic and tactile stimuli. We also show that repin intoxication reduces striatal and hippocampal GSH and increases total striatal dopamine (DA) levels in mice. Striatal microdialysis in rats, however, has demonstrated a significant reduction of extracellular DA levels. These findings, coupled with the absence of any demonstrable change in striatal DOPAC levels, suggest that repin acts by inhibiting DA release, a hypothesis that is further supported by our demonstration that, in cultured PC12 cells, repin inhibits the release of DA without affecting its uptake. We believe, therefore, that inhibition of DA release represents one of the earliest pathogenetic events in ENE, leading eventually to striatal extracellular DA denervation, oxidative stress, and degeneration of nigrostriatal pathways. Since the neurotoxic effects of repin appear to be mediated via oxidative stress, and since repin is a natural product isolated from a plant in our environment that can cause a movement disorder associated with degeneration of nigrostriatal pathways, clarification of the mechanism of repin neurotoxicity may provide new insights into our understanding of the pathogenesis of PD.
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PMID:Repin-induced neurotoxicity in rodents. 968 20

Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA synthesis step of DNA replication as well as nucleotide excision repair (NER) of damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA protein in the adult rat hippocampus following normo- and hypothermic global forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A constitutive expression of PCNA mRNA and protein was detected in all hippocampal subfields, as well as in other brain regions. During reperfusion, PCNA mRNA levels were up-regulated in the vulnerable CA1 subfield at 36 h following normothermic ischemia. In hypothermia, this induction appeared already after 18 h. Following normothermic ischemia, nuclear PCNA immunoreactivity was largely abolished during reperfusion in the vulnerable CA1 neurons, prior to cell death. In contrast, total PCNA protein content of this region, as measured by Western blotting, remained largely unchanged. In the CA3 region, a transient decrease in nuclear PCNA immunoreactivity was observed. In the dentate gyrus region, no down-regulation of nuclear or total PCNA protein was observed during reperfusion. Following hypothermic ischemia, the PCNA protein levels did not decrease in any of the hippocampal subregions. In contrast, no change in the levels of Ref-1, a protein involved in base excision DNA repair (BER), was observed following normo- or hypothermic ischemia. Our findings indicate an altered functional state of PCNA protein in the ischemia-sensitive CA1 neurons suggesting that DNA repair processes are affected in these post-mitotic cells following ischemia. Impaired DNA repair may play a role in the development of postischemic neuronal damage.
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PMID:Changes in proliferating cell nuclear antigen, a protein involved in DNA repair, in vulnerable hippocampal neurons following global cerebral ischemia. 975 27

Although hypothermia as a means of cerebral protection against and resuscitation from ischemic damage has a history of approximately six decades, extensive studies, both in basic and clinical fields, on the mechanisms, effects and methods of mild hypothermia at temperatures no less than 31 degrees C have started only in the last decade. In experiments on rodents, hypothermia in the postischemic period that is introduced up to several hours after reperfusion and is maintained for one day followed by a slow rewarming, significantly protects hippocampal neurons against damage. The mode of action of hypothermia is apparently non-specific and multi-focal in widely progressing cascade reactions in ischemic cells; namely, suppressing: (1) glutamate surge followed by; (2) intraneuronal calcium mobilization; (3) sustained activation of glutamate receptors; (4) dysfunction of blood brain barrier; (5) proliferation of microglial cells; and (6) production of superoxide anions and nitric oxide. In addition, mild hypothermia modulates processes in ischemic condition at the level of cell nucleus, such as the binding of transcription factor AP-1 to DNA, and ameliorates the depression of protein synthesis. This non-specific and widely affecting manner might explain why hypothermia is superior to any medicine developed. Recent clinical trials of mild hypothermia in various individual institutions have revealed significantly beneficial outcomes in some cases, along with an accumulation of practical knowledge of techniques and treatments. Large scale randomized studies involving multiple institutions as well as exchange of informations and ideas are needed for further development of hypothermia treatment.
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PMID:Mild hypothermia--a revived countermeasure against ischemic neuronal damages. 985 18

When cultured hepatocytes were incubated in cell culture medium at 4 degreesC for up to 30 h and then returned to 37 degreesC, blebbing of the plasma membrane, cell detachment, chromatin condensation and margination, enhanced nuclear stainability with Hoechst 33342, ruffling of the nuclear membrane, and DNA fragmentation occurred. Similar to hepatocytes, cultured liver endothelial cells exhibited blebbing, chromatin condensation and margination, marked nuclear condensation, and increased stainability with Hoechst 33342 when exposed to hypothermia/rewarming. In both cell types, the occurrence and extent of these alterations were dependent on the duration of the cold incubation period. This cold-induced apoptosis was inhibited by hypoxia, by an array of free radical scavengers/antioxidants, and by iron chelators. However, the extent of the protection by the different antioxidants was different in the two cell types: iron chelators provided complete protection in liver endothelial cells but only partial protection in hepatocytes, whereas lipophilic antioxidants such as alpha-tocopherol provided complete protection in both cell types. During cold incubation, and especially during rewarming, lipid peroxidation occurred. These results suggest that the formation of reactive oxygen species (ROS) is a key mediator of cold-induced apoptosis, with ROS formation being completely iron-mediated in liver endothelial cells and partially iron-mediated in hepatocytes.
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PMID:Cold-induced apoptosis in cultured hepatocytes and liver endothelial cells: mediation by reactive oxygen species. 987 40

Apoptosis plays a fundamental role in shaping normal hematopoiesis. We have investigated the relationship existing between susceptibility to apoptosis and lineage commitment in hemopoietic cells. The presence and degree of apoptosis were investigated in myeloid (HL-60 and K562), T (Jurkat and MOLT-4), and B (CESS and Raji) lymphoid cell lines by using a variety of techniques-transmission electron and light microscopy, flow cytometry and DNA gel electrophoresis. The major achievement of this study is that hematopoietic cells respond to different chemical (staurosporin, tiazofurin, camptothecin) and physical (hyperthermia or hypothermia) stimuli by apoptosis in a lineage-related way. Moreover, with respect to the methods used to detect apoptosis, a strong correlation was observed between the presence of the hypodiploid peak determined by flow cytometry and the DNA laddering evaluated by gel electrophoresis, but both techniques failed to demonstrate the presence of apoptosis in some cases. We conclude that cells of different hematopoietic lineages mostly show a lineage-related behaviour in their apoptotic response to different stimuli, suggesting that the lineage commitment and the stage of differentiation can confer different sensitivities to specific apoptotic stimuli. Moreover, morphological techniques still represent the most reliable approach to detect apoptosis in hemopoietic cells.
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PMID:Lineage-related susceptibility of human hemopoietic cell lines to apoptosis. 989 11

It has been repeatedly claimed that neuronal death in the hippocampal CA1 sector after untreated global ischemia occurs via apoptosis. This is based largely on DNA laddering, nick end labeling, and light microscopy. Delineation of apoptosis requires fine structural examination to detect morphological events of cell death. We studied the light and ultrastructural characteristics of CA1 injury after 5 min of untreated global ischemia in gerbils. To increase the likelihood of apoptosis, some ischemic gerbils were subjected to delayed postischemic hypothermia, a treatment that mitigates injury and delays the death of some neurons. In these gerbils, 2 d of mild hypothermia was initiated 1, 6, or 12 hr after ischemia, and gerbils were killed 4, 14, or 60 d later. Ischemia without subsequent cooling killed 96% of CA1 neurons by day 4, whereas all hypothermia-treated groups had significantly reduced injury at all survival times (2-67% loss). Electron microscopy of ischemic neurons with or without postischemic hypothermia revealed features of necrotic, not apoptotic, neuronal death even in cells that died 2 months after ischemia. Dilated organelles and intranuclear vacuoles preceded necrosis. Unique to the hypothermia-treated ischemic groups, some salvaged neurons were persistently abnormal and showed accumulation of unusual, morphologically complex secondary lysosomes. These indicate selective mitochondrial injury, because they were closely associated with normal and degenerate mitochondria, and transitional forms between mitochondria and lysosomes occurred. The results show that untreated global ischemic injury has necrotic, not apoptotic, morphology but do not rule out programmed biochemical events of the apoptotic pathway occurring before neuronal necrosis.
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PMID:Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia. 1034 Dec 24

The long-term effects of post-ischaemic hypothermia are controversial. The purpose of this study was to examine the long-term effects of post-ischaemic hypothermia on neuronal survival in gerbils in terms of morphology and function. Hypothermia was induced at 32 degrees C for 4 h immediately after ischaemia. Examination was performed at 1 week and at 1 month after ischaemia. Post-ischaemic hypothermia prevented CA1 neuronal damage 1 week after ischaemia. At 1 month after ischaemic insult, however, the degree of the protective effect of post-ischaemic hypothermia was reduced in the lateral and medial CA1 areas. DNA fragmentation was also observed at 1 month. The errors in the 8-arm radial maze trial were increased at 1 month. These data may indicate that cells in the CA1 area are very vulnerable to ischaemia and die after post-ischaemic hypothermia, and that their death is associated with apoptosis.
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PMID:The chronic cell death with DNA fragmentation after post-ischaemic hypothermia in the gerbil hippocampus. 1035 51

To characterize the development of tissue damage following cryogenic injury to the mouse cortex, the time course of histopathological changes, transcriptional responses and DNA strand breaks following application of a liquid nitrogen-cooled probe to the surface of the parietal bone were assessed. Distinct phases of tissue damage were observed: after 30 min, there was demarcation of a core lesion followed by mainly necrotic cell death starting 2 h after injury. At 12 hours, progressive apoptotic death of scattered cells in the periphery of the core lesion was detected, resembling the penumbra observed in ischaemic stroke. In situ hybridization for c-fos revealed an absence of expression in the core region, suggesting early cessation of transcription. There was strong induction of c-fos in the penumbra 30 min after the lesion, which had spread over the ipsilateral hemisphere at 2 h, possibly caused by peri-infarction depolarization. At later time points, sustained expression of c-fos was observed in some cells in the penumbra. Since a role for c-fos has been postulated in the initiation or execution of apoptotic pathways, the susceptibility of c-fos deficient mice was explored (n=4) in this model. Cryoinjury-induced tissue injury was markedly attenuated in c-fos deficient mice. A model of the phases and mechanisms of cryogenic injury is proposed, which discriminates an early phase characterized by physical changes caused by hypothermia and their immediate consequences (i.e. transcriptional block), an intermediate phase where secondary changes lead to necrosis in the core region, and a final phase of delayed apoptotic cell death in the penumbra.
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PMID:Distinct phases of cryogenic tissue damage in the cerebral cortex of wild-type and c-fos deficient mice. 1063 97


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