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

Hypothermia is known to be the most effective method to protect the neuronal damage induced by ischemia. In the present study, we investigated the histopathological consequences of hippocampal CA1 pyramidal neurons as well as the glial reactions in the hippocampus, after diverse periods of ischemic insult at graded intra-ischemic hypothermia ranging from 32 to 20 degrees C. Gerbils were exposed to forebrain ischemia by clamping the bilateral common carotid arteries for 5-120 min depending upon the temperatures. The morphological study was performed 7 days after ischemia or sham-operation. Histopathological evaluation of delayed neuronal death (DND) was performed by Cresyl violet (CV) staining and MAP2 immunoreactivity. Glial reactions were examined by GFAP immunostaining and isolectin B4 histochemistry, corresponding to astrocytes and microglia, respectively. The forebrain ischemia at 32 degrees C for 10 min and at 28 degrees C for 20 min did not induce DND in the CA1 region. However, the ischemia at 32 degrees C for 20 min and at 28 degrees C for 30 min caused extensive degeneration of CA1 pyramidal neurons as observed in normothermic ischemic animals. Under the condition of deep hypothermia, the ischemia for 60 min at 24 degrees C and for 120 min at 20 degrees C which were the longest durations of each temperature within the limitation of the animal survival following 7 days, induced no DND in CA1 pyramidal neurons. The reactive changes of astrocytes were observed not only in ischemic animals with DND, but also in ischemic animals without DND. Computer image analysis showed that the area fraction of GFAP-positive structures in the CA1 region was significantly increased in both ischemic cases with and without DND compared with each sham group. In contrast, the distribution of activated microglia was much more restricted to the CA1 region and they were always accompanied by DND at 7 days postischemia. The present results demonstrate the remarkable neuroprotective effect of deep hypothermia that has been widely used in cardiovascular surgeries as the cerebroprotective strategy during total circulatory cessation. The findings also suggest that even under the condition of hypothermia, glial reactions may play an important role in neuronal survival and death after ischemia.
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PMID:Morphological investigation of the neuroprotective effects of graded hypothermia after diverse periods of global cerebral ischemia in gerbils. 931 Apr 1

We examined whether mild brain hypothermia during pretreatment with sublethal 2-min ischemia affected the tolerance to subsequent lethal 5-min ischemia. The neuronal densities in the hippocampal CA1 sector of gerbils preconditioned at mild brain hypothermia (32% of normal) were significantly lower than those in gerbils preconditioned at brain normothermia (70% of normal). 72-kDa heat-shock protein immunoreactivity in the CA1 sector preconditioned at mild hypothermia was reduced. These results suggest that mild brain hypothermia during pretreatment with sublethal ischemia reduces the tolerance to subsequent lethal ischemia.
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PMID:Intraischemic hypothermia during pretreatment with sublethal ischemia reduces the induction of ischemic tolerance in the gerbil hippocampus. 941 39

Novel antagonists of the glycineB site of the NMDA receptor (MRZ 2/570, MRZ 2/576), and an AMPA receptor antagonist, NBQX were tested in 3-min global ischaemia in gerbils. Untreated animals showed after 14 days a loss of almost 90% of pyramidal neurones in the CA1 region, which was prevented by NBQX, and reduced to 50% by both glycineB antagonists. NBQX produced a delayed, long lasting (up to 24 hr) hypothermia while hypothermia with both glycineB antagonists was transient.
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PMID:Protection against post-ischaemic neuronal loss in gerbil hippocampal CA1 by glycineB and AMPA antagonists. Short communication. 950 69

A number of experimental studies have reported that moderate hypothermia can produce significant protection against behavioral deficits and/or morphopathological alterations following traumatic brain injury; a Phase 3 clinical trial is currently examining the therapeutic potential for moderate hypothermia (32 degrees C) to improve outcome following severe traumatic brain injury in humans. The current study examined whether hypothermia (32 degrees C) provided behavioral protection following experimental cortical impact injury. The extent of focal cortical contusion was also examined in the same rats. A total of 30 male Sprague-Dawley rats were trained on beam balance and beam walking tasks prior to injury. Under isoflurane anesthesia, cortical impact was produced on the right parietal cortex of 20 rats. Ten rats underwent all surgical procedures but were not impacted (sham-injured rats). Ten of the injured rats were cooled to 32 degrees C (measured in temporalis muscle) beginning 5 min postinjury, maintained for 2 h and rewarmed slowly for 1 h. In the other 10 injured rats, normothermic temperatures (37.5 degrees C) were maintained for the same duration. Beam balance and beam walking performance was assessed daily for 5 days following injury. At 11 days postinjury, rats were assessed for 5 days on acquisition of the Morris water maze task. Following behavioral assessments, rats were perfused and the brain removed. Coronal sections were cut through the site of cortical impact injury and stained with hematoxylin and eosin. Hypothermic treatment resulted in significantly less beam balance and beam walking deficits than observed in normothermic rats. Hypothermia also significantly attenuated spatial memory performance deficits. Quantitative morphometric analyses failed to detect any significant differences in volumes of necrotic tissue cavitation in cortices of hypothermic and normothermic rats. Hypothermic treatment also had no effect on volumes of dorsal hippocampal tissue or numbers of cells in CA1 or CA3 regions of the hippocampus. These data suggest that hypothermia, consistent with the reports of others, can produce significant behavioral protection following cortical impact injury that is not necessarily correlated with changes in focal cortical necrosis within the first 15 days following injury.
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PMID:Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat. 951 85

To estimate whether mild hypothermia during repetitive hypoxia provides a neuroprotective effect on brain tissue, hippocampal slice preparations were subjected to repetitive hypoxic episodes under different temperature conditions. Slices of guinea pig hippocampus (n=40) were placed at the interface of artificial cerebrospinal fluid (aCSF) and gas (normoxia: 95% O2, 5% CO2; hypoxia: 95% N2, 5% CO2). Evoked potentials (EP) and direct current (DC) potentials were recorded from hippocampal CA1 region. Slices were subjected to two repetitive hypoxic episodes under the following temperature conditions: (A) 34 degrees C/34 degrees C, (B) 30 degrees C/30 degrees C and (C) 34 degrees C/30 degrees C. Hypoxic phases lasted until an anoxic terminal negativity (ATN) occurred. The recovery after first hypoxia lasted 30 min. Tissue function was assessed regarding the latency of ATN and the recovery of evoked potentials. The ATN latencies with protocol A (n = 25) for the first and second hypoxia were 5.9+/-1.3 min (mean+/-S.E.M., 1st hypoxia) and 2.4+/-0.9 min (2nd hypoxia), with protocol B the latencies (n = 7) were significantly longer: 25.2+/-7.1 min and 15.6+/-7.7 min. With protocol C (n=8), the latencies were 5.6+/-1.8 and 3.3+/-0.5 min. No differences were seen in the recovery of the EPs with protocols A-C. Our results suggest that a mild hypothermia is only neuroprotective if applied from an initial hypoxia onwards.
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PMID:Neuroprotection of mild hypothermia: differential effects. 955 52

In order to examine the effects of hypothermia on the changes in membrane potential induced by experimental ischemia (deprivation of oxygen and glucose), intracellular recordings were made from single CA1 pyramidal neurons in slice preparations of rat hippocampus. Application of ischemic medium caused irreversible changes in membrane potential consisting of an initial hyperpolarization, then a slow depolarization and a rapid depolarization. At temperatures of 35 degrees C and 37 degrees C, once the rapid depolarization occurred, readministration of oxygen and glucose failed to restore the membrane potential, a state referred to as irreversible membrane dysfunction. When the temperature was lowered to between 27 degrees C and 33 degrees C, the membrane potential returned to the control resting membrane potential in 75% of the neurons. The temperature coefficients (Q10) of the latency, the amplitude, and the maximal slope of the rapid depolarization were 2.5, 1.4 and 2.9, respectively. It is concluded that the critical neuroprotective temperature in ischemia-induced membrane dysfunction is found to be 33 degrees C in single CA1 neurons in vitro.
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PMID:Mild hypothermia protects rat hippocampal CA1 neurons from irreversible membrane dysfunction induced by experimental ischemia. 957 74

The ability of diazepam, a benzodiazepine full agonist, and imidazenil, a benzodiazepine partial agonist, to protect hippocampal area CA1 neurons from death for at least 35 days after cerebral ischemia was investigated. Diazepam (10 mg/kg) administered to gerbils 30 and 90 minutes after forebrain ischemia produced significant protection of hippocampal area CA1 pyramidal neurons 7 days later. In gerbils surviving for 35 days, diazepam produced the same degree of neuroprotection (70% +/- 30%) in the hippocampus compared with 7 days after ischemia. The therapeutic window for diazepam was short; there was no significant neuroprotection when the administration of diazepam was delayed to 4 hours after ischemia. The neuroprotective dose of diazepam also produced hypothermia (approximately 32 degrees C) for several hours after injection. To assess the role of hypothermia in neuroprotection by diazepam, hypothermia depth and duration was simulated using a cold-water spray in separate gerbils. Seven days after ischemia, neuroprotection by hypothermia was similar to that produced by diazepam. However, 35 days after ischemia, there was no significant protection by hypothermia, suggesting that hypothermia does not play a significant role in long-term diazepam neuroprotection. Imidazenil (3 mg/kg), which produced only minimal hypothermia, protected area CA1 of hippocampus to the same degree as that by diazepam 7 days after ischemia. At 35 days after ischemia, significant protection remained, but it was considerably reduced compared with 7 days. Like diazepam, the therapeutic window for imidazenil was short. Imidazenil neuroprotection was lost when the drug was administered as early as 2 hours after ischemia. The ability of ischemia to produce deficits in working memory and of benzodiazepines to prevent the deficits also was investigated. Gerbils trained on an eight-arm radial maze before ischemia demonstrated a significant increase in the number of working errors 1 month after ischemia. The ischemia-induced deficits in working memory were completely prevented by diazepam but not by imidazenil. There was a significant, but weak, negative correlation between the degree of CA1 pyramidal cell survival and the number of working errors in both the diazepam and imidazenil groups. Thus, if given early enough during reperfusion, both benzodiazepine full and partial agonists are neuroprotective for at least 35 days, but the lack of sedating side effects of imidazenil must be weighed against its reduced efficacy.
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PMID:Long-term neuroprotection by benzodiazepine full versus partial agonists after transient cerebral ischemia in the gerbil [corrected]. 959 47

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

Recent studies have demonstrated the neuroprotective properties of the novel imidazoquinoline benzodiazepine receptor partial agonist, PNU-101017, in the gerbil forebrain ischemia model. The compound effectively reduces delayed post-ischemic (5 min bilateral carotid occlusion) hippocampal CA1 neuronal degeneration even when its administration is withheld until 4 h after reperfusion and the effect is unrelated to hypothermia. The purpose of the present study was to determine the comparative abilities of PNU-101017 versus the full agonist diazepam to attenuate post-ischemic CA1 damage. Male gerbils were treated either 30 min before ischemia induction or immediately after reperfusion with an initial dose of PNU-101017 (30 mg/kg i.p.) or diazepam (10 mg/kg i.p.) with a second dose being given at 2 h after reperfusion. Possible hypothermic effects of either compound were prevented by external heating. In vehicle (0.05 N HCl)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 85%. PNU-101017 pretreatment reduced the loss to 50% (p<0.05 vs. vehicle) whereas pretreatment with diazepam attenuated damage to only 17% (p<0.001 vs. vehicle). Delaying treatment with PNU-101017 until just after reperfusion still resulted in a reduction in CA1 degeneration statistically that was indistinguishable from that seen with pretreatment. In contrast, diazepam post-treatment did not significantly decrease CA1 neuronal loss. These results suggest that a benzodiazepine receptor partial agonist may have greater neuroprotective practicality than a full agonist for the treatment of global cerebral ischemia. The mechanistic basis for this difference may relate to the partially pro-excitatory neuronal response to endogenous GABA before and after neuronal insult.
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PMID:Comparative neuroprotective properties of the benzodiazepine receptor full agonist diazepam and the partial agonist PNU-101017 in the gerbil forebrain ischemia model. 966 60

Disturbances in neuronal communication induced by rapid temperature changes are a risk in the context of accidental hypothermia and would be fatal for hibernators during arousal from hibernation. Therefore, we investigated the effects of rapid temperature changes on synaptically induced CA1 population spikes in hippocampal slices from golden hamsters (hibernators) and rats (non-hibernators). Temperature was changed ramp-like by 0.3 degrees C/min, which corresponds to the rise of body temperature in golden hamsters during arousal from hibernation. During cooling from 35 to 10-15 degrees C, the population spike amplitude increased, reached maximal values at 25-30 degrees C and 20-25 degrees C in hamster and rat slices, respectively, and then decreased with further cooling. During rewarming, hamster slices displayed the same temperature dependence as during cooling. In contrast, in rat slices dynamic effects of the temperature change occurred. These were most obvious in a strong depression of the spike amplitude during rewarming as compared to cooling. Above 26-29 degrees C, the depression was superimposed by an excitatory effect. The depression was largely attenuated by theophylline (100-200 microM) and thus seems to be based on an increase of the concentration of endogenous adenosine, which in turn may result from an imbalance in energy metabolism during warming. The lack of warming-related depression in hamster slices can be explained by a lower sensitivity for adenosine as compared to rat slices. In addition, a better resistance of metabolic balance against rapid temperature changes may prevent large elevations of endogenous adenosine in the hamster hippocampus. For hibernators, the avoidance of temperature change-induced disturbances of neuronal communication may be a prerequisite for safe arousal from hibernation.
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PMID:Rapid temperature changes induce adenosine-mediated depression of synaptic transmission in hippocampal slices from rats (non-hibernators) but not in slices from golden hamsters (hibernators). 969 44


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