Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we sought to determine the optimal brain temperature for treating compression-induced cerebral ischemia. Six cats each were treated with a deep-brain temperature of 37 degrees C (control), 33 degrees C (mild hypothermia), or 29 degrees C (moderate hypothermia). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, as were arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2). The cerebral metabolic rate of oxygen (CMRO2) was calculated. Extracellular glutamate concentration was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero. This ischemia was maintained for 5 min, after which the balloon was deflated. Mild hypothermia showed coupled CBF-metabolic suppression, but moderate hypothermia resulted in disproportionately increased AVDO2, decreased ScvO2, and low CBF/CMRO2 (relative ischemia). Reactive hyperemia after balloon deflation was decreased after both mild and moderate hypothermia, as was the tissue volume showing Evans blue dye extravasation. Extracellular glutamate increased in control animals, an effect most effectively suppressed in the mild hypothermia group. These data favor 33 degrees C as the optimal temperature for treating compression-related cerebral ischemia.
 ...
PMID:Effects of mild and moderate hypothermia on cerebral metabolism and glutamate in an experimental head injury. 977 90

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.
 ...
PMID:Mild hypothermia--a revived countermeasure against ischemic neuronal damages. 985 18

The effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia were investigated to determine which temperature was more effective against compression-induced cerebral ischemia. Eighteen cats were anesthetized. The animals were divided into three groups according to deep-brain temperature (control, 37 degrees C; mild hypothermia, 33 degrees C; and moderate hypothermia, 29 degrees C). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, the latter by hydrogen clearance. Arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO2) and the cerebral metabolic rate of lactate (CMR lactate) were calculated. Extracellular glutamate was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero, and this ischemia was maintained for 5 min, after which the balloon was quickly deflated. All parameters were recorded over 6 h. Evans blue was injected to examine vascular permeability changes. CBF was decreased by 56% by mild hypothermia and by 77% by moderate hypothermia. Mild hypothermia had a coupled metabolic suppression whereas moderate hypothermia significantly increased AVDO2 and decreased ScvO2, producing a low CBF/CMRO2 (relative ischemia). After balloon deflation, all three groups showed reactive hyperemia, which was significantly reduced by mild and moderate hypothermia. CBF then decreased to 50% of pre-inflation values and ScvO2 decreased (post-ischemic hypoperfusion). CBF/CMRO2, ScvO2, and AVDO2 did not differ significantly between the three groups. After balloon deflation, all three groups showed increased CMR lactate, which was significantly reduced by mild and moderate hypothermia. Extracellular glutamate increased in control animals (3.8 +/- 1.72 microM), an effect most effectively suppressed in the mild hypothermia group (1.0 +/- 0.46 microM). Damaged tissue volumes as indicated by Evans blue dye extravasation were 729 +/- 89 mm3 in control, 247 +/- 56 mm3 in mild hypothermia, and 267 +/- 35 mm3 in moderate hypothermia animals. These data suggest that mild hypothermia (33 degrees C) might be the optimal brain temperature to treat compression-related cerebral ischemia.
 ...
PMID:Effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia on cerebral blood flow and metabolism, lactate, and extracellular glutamate in experimental head injury. 986 37

Using a dialysis electrode, we recently developed an oxygen-independent system for real-time measurement of the glutamate concentration in the extracellular space ([Glu]e) during ischemia. This system allows separate evaluation of intra-ischemic biphase [Glu]e elevation, i.e. release from synaptic vesicles (1st phase), reversed uptake of glutamate from metabolic pools in neuronal cells (2nd phase), and post-ischemic glutamate re-uptake in ischemia-reperfusion models. Using the system, we attempted to clarify the relationship between biphase glutamate release and brain temperature in a model of acute global ischemia produced by transecting both carotid arteries. Our results showed that, in contrast to mild hyperthermia, hypothermia did not inhibit the 1st phase of [Glu]e release, and changes in intra-ischemic brain temperature had a minimal effect on the 2nd phase of [Glu]e elevation during severe acute ischemia. These findings, together with our previous data, indicate that brain temperature change in the intra-ischemic period plays an important role in disturbance of the glutamate re-uptake system during ischemia.
 ...
PMID:Minimal effect of brain temperature changes on glutamate release in rat following severe global brain ischemia: a dialysis electrode study. 987 19

Incubation of rat striatal slices in the absence of oxygen (anoxia), glucose (aglycemia), or oxygen plus glucose (ischemia) caused significant increases in dopamine (DA) release. Whereas anoxia decreased extracellular 3,4-dihydroxyphenylacetic acid levels by 50%, aglycemia doubled it, and ischemia returned this aglycemia-induced enhancement to its control level. Although nomifensine, a DA uptake blocker, completely protected the slices against anoxia-induced DA depletion, aglycemia- and ischemia-induced increases were not altered. Moreover, hypothermia differentially affected DA release stimulated by anoxia, aglycemia, and ischemia. Involvement of glutamate in DA release induced by each experimental condition was tested by using MK-801 and also by comparing the glutamate-induced DA release with that during anoxia, aglycemia, or ischemia. MK-801 decreased the anoxia-induced DA depletion in a dose-dependent manner. This treatment, however, showed a partial protection in aglycemic conditions but failed to improve ischemia-induced DA depletion. Like anoxia, DA release induced by exogenous glutamate was also sensitive to nomifensine and hypothermia. These results indicate that anoxia enhances DA release by a mechanism involving both the reversed DA transporter and endogenous glutamate. Partial or complete lack of effect of nomifensine, hypothermia, or MK-801 in the absence of glucose or oxygen plus glucose also suggests that experimental conditions, such as the degree of anoxia/ischemia, may alter the mechanism(s) involved in DA depletion.
 ...
PMID:Anoxia-induced dopamine release from rat striatal slices: involvement of reverse transport mechanism. 1009 55

The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.
 ...
PMID:Brain temperature modifies glutamate neurotoxicity in vivo. 1022 15

Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4 beta-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 mumol/L to an end ischemic level of 4.8 mumol/L during hypothermic ischemia (33 degrees C). These levels were significantly higher than in hypothermic ischemia (33 degrees C) without added PDBu. Staurosporine significantly mitigated the glutamate levels during normothermic ischemia. Our data suggest that PKC is involved in the temperature-dependent elevations of extracellular glutamate levels in the striatum during ischemia, and we propose that compounds preventing PKC activation may mimic the hypothermic protective action against ischemic brain damage.
 ...
PMID:The effect of 4 beta-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum. 1034 75

An exogenous glutamate injection into the hypothermic hippocampal CA1 during 5-min ischemia produced the same extent of extracellular glutamate levels as observed in the normothermic CA1 during 5-min ischemia; however, neuronal death was not induced in the hypothermic CA1. Glutamate is released excessively into the extracellular space during ischemia, and is thought to induce brain injury by its neurotoxicity. It has been reported that the massive glutamate release is reduced by mild hypothermia, and it has been proposed that the reduction of ischemia-induced glutamate release exerts the neuroprotective effect on postischemic neuronal death. In the present study, to determine whether the neuroprotective effect of mild hypothermia on postischemic hippocampal CA1 neuronal death is due to the reduction of ischemia-induced glutamate release, gerbils were subjected to 5-min ischemia under hypothermic condition at 31 degrees C and were simultaneously injected exogenously with L-glutamate, so that the hypothermic CA1 around a microdialysis probe was exposed to the same extracellular glutamate levels as seen during normothermic ischemia, and the histological outcome was examined. An injection with 1 mM L-glutamate into the hypothermic CA1 during 5-min ischemia produced a similar extent of increased glutamate (17-fold increase) to that observed in the normothermic CA1 during 5-min ischemia (16-fold increase). However, neuronal death was not induced in the hypothermic CA1. This result indicates that the neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia.
 ...
PMID:Neuroprotective effect of mild hypothermia cannot be explained in terms of a reduction of glutamate release during ischemia. 1036 7

During cerebral ischaemia, energetic failure of injured cells together with excessive release of glutamate the most common excitatory amino acid in the brain, lead to excitotoxicity and immediate or delayed neuronal death. There is strong experimental evidence to support the neuroprotective role played by anaesthetic agents. Hence, barbiturates, volatile anesthetics or ketamine exhibit significant protective effects against ischaemic injury in numerous experimental models of ischaemia in vitro or in vivo. The neurobiological substrate of this action is probably a reduction of the activity of glutamate receptors (N-methyl-D-aspartate and kainate), and/or downstream biochemical events. Reduction of cerebral metabolism by these agents seems not to be their primary neuroprotective mechanism. However, no data are available at the present time to support any clinical benefit of these actions in neurosurgical patients, head trauma in contrast to mild hypothermia or cerebrovascular disease. Future research should develop models as close as possible to the clinical situation to examine further pathophysiological hypotheses and clinical implications.
 ...
PMID:[Neuroprotective effects of anesthetics]. 1042 97

It has previously been shown that hypothermia markedly reduces cellular release of the excitatory amino acid glutamate and ameliorates ischemic damage. Based on extensive data showing that preischemic hyperglycemia exaggerates brain damage due to transient forebrain ischemia we posed the question whether glutamate release during ischemia in hyperglycemic rats is attenuated or prevented by induced hypothermia, and if such attenuation/prevention correlates with amelioration of the characteristic brain damage observed in hyperglycemic subjects. The experiments were performed in rats subjected to a 15-min period of forebrain ischemia, plasma glucose concentration being maintained at approximately 5 mM (control) or approximately 20 mM (hyperglycemia) prior to ischemia. Extracellular amino acid concentrations were measured by HPLC techniques on microdialysis samples which were collected from left dorsal hippocampus and right neocortex, and tissue damage was assessed by histopathology. Hypothermia (30 degrees C), which was induced 45 min prior to ischemia, reduced the neuronal damage not only in the ischemia-vulnerable regions but also in the normally ischemia-resistant areas that are recruited in the damage process in hyperglycemic subjects. The extracellular glutamate concentration was markedly increased in response to the ischemic insult in normothermic-normoglycemic animals. The concentration of glutamate was further increased in normothermic-hyperglycemic animals. Hypothermia inhibited the rise in glutamate concentrations, as well as in the concentrations of other excitatory and inhibitory amino acids. It is discussed whether hypothermia reduces the hyperglycemia-mediated damage by inhibiting extracellular glutamate release during an ischemic transient.
 ...
PMID:Hypothermia ameliorates ischemic brain damage and suppresses the release of extracellular amino acids in both normo- and hyperglycemic subjects. 1044 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>