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

This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intraischemic rectal temperature was either maintained at 36-37 degrees C or allowed to fall passively to 28-32 degrees C. Antagonists and doses tested were 1 and 10 mg/kg of MK-801 (pre- or postischemia), 30 mg/kg of CGS 19755 preischemia, four 25 mg/kg doses of CGS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre- or postischemia). All three NMDA receptor antagonists exhibited some degree of neuroprotective activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CA1 hippocampal and neocortical pyramidal cells were spared by only three of the treatments, however, and the extent of neuroprotection varied widely from case to case. Toxic doses of antagonist were required to protect CA1 pyramidal cells from ischemic damage. Ischemic damage to hippocampal areas CA2-CA3a and CA4 appeared to be resistant to all of these treatments. Most CA1 pyramidal cells that were protected from degeneration by an NMDA receptor antagonist were histologically abnormal. The neuroprotective effects of MK-801 and intraischemic hypothermia appeared to be additive. MK-801 (10 mg/kg) consistently reduced the postischemic brain temperature, but only the magnitude of hypothermia produced soon after reperfusion correlated with its neuroprotective action. These results suggest that NMDA receptor antagonists are relatively poor neuroprotective agents against a moderately severe ischemic insult.
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PMID:Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil. 182 9

Cerebral ischemia produces a disruption of calcium homeostasis in neurons. This may explain the extreme sensitivity of these cells to ischemic insult. Prolonged increases in calcium levels may produce irreversible damage to the cell by altering important calcium-dependent enzyme systems such as calcium/calmodulin-dependent protein kinase II. Five minutes of acute forebrain ischemia in the gerbil produced a significant decrease in calcium/calmodulin-dependent protein kinase II activity as early as 10 seconds postischemia and persisting up to 7 days after insult. Because hypothermia protects against ischemia-induced cell death in the gerbil, we examined the effect of ischemia on cell death and calcium/calmodulin-dependent protein kinase II at different intracerebral temperatures: hyperthermia (39 degrees C), normothermia (36 degrees C), and hypothermia (32 degrees C). In ischemic animals, hyperthermia produced severe loss of neurons in CA1 and moderate loss in CA3-CA4 subregions. Normothermia in ischemic animals produced severe loss of neurons in the CA1 subregion. Hypothermic ischemic animals showed no significant loss of neurons in any hippocampal region. Ischemia produced a severe decrease (17 +/- 6% of control) in calcium/calmodulin-dependent kinase II activity in hyperthermic animals, a moderate decrease (55 +/- 15% of control) in normothermic animals, and no decrease of enzyme activity in hypothermic animals. Thus, lowering and raising intracerebral temperature decreased and increased, respectively, the extent of ischemia-induced damage in the gerbil. Because ischemia-induced effects on calcium/calmodulin-dependent protein kinase II activity are rapid and long-lasting, hypothermia may protect through preservation of calcium/calmodulin-dependent protein kinase II activity.
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PMID:Effects of ischemia on multifunctional calcium/calmodulin-dependent protein kinase type II in the gerbil. 217 73

We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1 pyramidal neurons measured 7 days after ischemia (28.4 neurons/mm, n = 10; control density in 10 naive gerbils 262.1 neurons/mm) and a significant decrease in forebrain calcium/calmodulin-dependent protein kinase II autophosphorylation measured 2 hours after ischemia (12.9 fmol/min, n = 6; control phosphorylation in six naive gerbils 23.5 fmol/min). The effect of temperature on these indicators of ischemic damage was examined by adjusting intracerebral temperature before and during the ischemic insult. Hyperthermic (39 degrees C) gerbils showed almost complete loss of neurons in the CA1 region (3.0 neurons/mm, n = 11) and extension of neuronal death into the CA2, CA3, and CA4 regions. In addition, hyperthermia exacerbated ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity (4.2 fmol/min, n = 6). Hypothermia (32 degrees C) protected against ischemia-induced CA1 pyramidal cell damage (257.0 neurons/mm, n = 20) and inhibition of calcium/calmodulin-dependent protein kinase II activity (26.0 fmol/min, n = 6). Our results are consistent with the hypothesis that loss of calcium/calmodulin-dependent protein kinase II activity may be a critical event in the development of ischemia-induced cell death.
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PMID:Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils. 226 78

Repetitive ischemia may result in more severe damage than a single similar duration insult. Inter-ischemic hypothermia significantly decreases this damage. It is unclear if protection would be evident if cooling was delayed until after the repeated insults. In this study, we evaluated the effects of 3 h of mild cooling (34-35 degrees C) beginning immediately after the third insult of ischemia, 0.5 h after the third insult and 1 h after the third insult in a gerbil model of repetitive ischemia. Neuronal damage was assessed in the cerebral cortex (CTX), hippocampus (CA1, CA4), striatum (STR), thalamus (THL), medial geniculate nucleus (MGN), and the substantia nigra reticulata (SNr). A '4-point' damage scale was used and evaluation was done in a blinded way. Group comparisons were done using the Mann-Whitney U-test for significance between the control and hypothermic groups. Immediate hypothermia after the third ischemic insult produced a significant protection in the CTX (P < 0.05), hippocampus (CA1 and CA4, P < 0.01), STR (P < 0.001), SNr (P < 0.01), MGN (P < 0.01) and THL (P < 0.01). Cooling at 0.5 and 1 h after the third insult produced no protection when compared to ischemic controls. The window of opportunity with hypothermia is narrow in repetitive ischemia. To be effective, therapy must be initiated as soon as possible after ischemic insults.
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PMID:The effect of post-ischemic hypothermia following repetitive cerebral ischemia in gerbils. 777 88

The purposes of this study were (1) to document the histopathological consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats, and (2) to determine whether post-traumatic brain hypothermia (30 degrees C) would protect histopathologically. Twenty-four hours prior to TBI, the fluid percussion interface was positioned over the right cerebral cortex. On the 2nd day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37.5 degrees C), rats were injured with a fluid percussion pulse ranging from 1.7 to 2.2 atmospheres. In one group, brain temperature was maintained at normothermic levels for 3 h after injury. In a second group, brain temperature was reduced to 30 degrees C at 5 min post-trauma and maintained for 3 h. Three days after TBI, brains were perfusion-fixed for routine histopathological analysis. In the normothermic group, damage at the site of impact was seen in only one of nine rats. In contrast, all normothermic animals displayed necrotic neurons within ipsilateral cortical regions lateral and remote from the impact site. Intracerebral hemorrhagic contusions were present in all rats at the gray-white interface underlying the injured cortical areas. Selective neuronal necrosis was also present within the CA3 and CA4 hippocampal subsectors and thalamus. Post-traumatic brain hypothermia significantly reduced the overall sum of necrotic cortical neurons (519 +/- 122 vs 952 +/- 130, mean +/- SE, P = 0.03, Kruskal-Wallis test) as well as contusion volume (0.50 +/- 0.14 vs 2.14 +/- 0.71 mm3, P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat. 800 57

In small animals the damaging effects of repetitive ischemia are more severe than a single insult of similar duration. Prolonged release of glutamate may correlate with the degree of damage. We report the protective effects of CGS-19755 (an N-methyl-D-aspartate receptor blocker), hypothermia or CGS-19755 in combination with mild hypothermia, in a gerbil model of repetitive ischemia. We used 3 min of forebrain ischemia and repeated it for a total of three times as 1-h intervals. Damage was assessed seven days after the insult. In the group where only CGS-19755 was used, significant neuronal protection was evident in the hippocampus (CA1 and CA3), striatum, and medial geniculate nucleus. With hypothermia significantly less damage was seen in the cerebral cortex, hippocampus (CA1 and CA4), and substantia nigra reticulata. When CGS-19755 was combined with mild hypothermia the effects of repetitive ischemia were completely abolished in all but one gerbil. Compared to hypothermia alone, significant protection was seen in the cerebral cortex, hippocampus (sibiculum, CA1 and CA4), striatum, medial geniculate nucleus, thalamus, and substantia nigra reticulata. The use of N-methyl-D-aspartate receptor blockers may protect the brain in repetitive ischemia. Combination with hypothermia may further enhance this protection.
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PMID:CGS-19755 is neuroprotective during repetitive ischemia: this effect is significantly enhanced when combined with hypothermia. 828 43

The protective effect on ischemic hippocampal damage was compared between intra- and postischemic hypothermia in Mongolian gerbils and its regional preference was evaluated. Male Mongolian gerbils were subjected to transient forebrain ischemia and the hippocampus 7 days after ischemia was examined histologically. In the intraischemic hypothermia (29-31 degrees C) group, CA1 damage was completely prevented in spite of spontaneous postischemic hyperthermia. In contrast, the same degree of brief postischemic hypothermia exerted no preventive effect. While neurons in the subiculum and CA2 sector were also protected against ischemic damage by intraischemic hypothermia, injured pyramidal neurons were always seen in the CA4 sector.
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PMID:Hypothermic prevention of the hippocampal damage following ischemia in Mongolian gerbils comparison between intraischemic and brief postischemic hypothermia. 844 93

A recent study showed that a single intracarotid arterial injection of cyclosporin A (CsA) can dramatically reduce infarct volume in rats subjected to transient focal ischemia. The present experiments were undertaken to investigate whether intracarotid arterial injection of CsA reduces brain damage after global ischemia. Since hypothermia is also an efficacious factor in preventing ischemic brain damage, in the second part of the experiments we tested whether a combination of hypothermia and CsA would provide additional brain protection. Global ischemia of a 30-min duration was induced in the rat. CsA (10 mg/kg) was injected into the carotid artery immediately after reperfusion. Hypothermia was instituted after ischemia by allowing spontaneous head temperature to fall to 30-32 degrees C, while body temperature was upheld at 37 degrees C. The results demonstrated that vehicle-treated animals could not survive beyond 1-2 days after reperfusion, and the histopathological outcome in a separate group of rats perfusion-fixed after 1 day reperfusion showed 80-100% brain damage in the caudoputamen, and in the hippocampal CA1, CA3, CA4 and dentate gyrus subregions. Microinfarction and grade 3 damage were frequently observed in the cingulate and parietal cortex and in the thalamus. CsA moderately prolonged animal survival to 3 days after reperfusion and reduced brain damage to grade 2 in the cortical areas and the thalamus. Hypothermia further increased animal survival to at least 6 days after reperfusion and reduced brain damage to 30% in the caudoputamen, to close to zero in the CA3, CA4, and dentate gyrus, and to grade 1-2 in the cortical areas and the thalamus. The combination of hypothermia and CsA did not give additional protection.
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PMID:Effects of intracarotid arterial injection of cyclosporin A and spontaneous hypothermia on brain damage incurred after a long period of global ischemia. 1116 97

The acute effects of ultraprofound hypothermia and blood substitution (UHBS) on neuronal cell viability were examined in adult rat hippocampus, a brain region particularly vulnerable to ischemic cell death. UHBS was performed using either artificial cerebrospinal fluid (ACSF) or Hypothermosol, an "intracellular-type" hypothermic preservation solution. After the procedure, the hippocampus was sliced and tested for cellular viability using a combination of cellular fluorochromes that are markers for live cells (acridine orange) and dead cells (propidium iodide). UHBS with ACSF resulted in a variable degree of neuronal death within the hippocampal subfields CA1/CA3, and dentate granular layer and hilus (CA4). In contrast, UHBS with Hypothermosol consistently resulted in hippocampal slices with only mild neuronal death. Our results of preserved hippocampal neuronal viability with use of UHBS and Hypothermosol support the demonstrated central nervous system (CNS) protective effects of UHBS and Hypothermosol when used during prolonged cardiac arrest. The results of this study also suggest that UHBS and Hypothermosol may be useful in the preparation and maintenance of viable hippocampal tissue for physiological studies, especially those involving aged animals, which are particularly vulnerable to hypoxic-ischemic cellular injury
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PMID:Ultraprofound cerebral hypothermia and blood substitution with an acellular synthetic solution maintains neuronal viability in rat hippocampus. 1178 40

The objective of this study was to evaluate the effects of a moderate, intraischemic hypothermia on the behavorial deficits up to 4 weeks after induction of a focal mass lesion. A focal epidural mass lesion was induced by an epidural balloon. The severity of the trauma was defined by the balloon volume and flattening of electroencephalography. Hypothermia (32 degrees C) was induced as soon as maximum balloon infIation was reached. Ischemia was extended over 30 min. After reperfusion, normothermic (n = 24) and hypothermic animals (n = 25) were monitored for 3 h followed by a rewarming of the cooled animals. Results were compared to sham-operated animals (n = 10). Behavioral deficits were assessed by postural reflex (PR), open field (OF), beam balance (BB), beam walking (BW), and water maze tests (WMT). MRI follow-up and histology was evaluated. Sham-operated rats showed normal test results. Rats with normothermia showed worsening of test performance (PR, p < 0.05; OF, p < 0.05; BB, p < 0.05; BW, p < 0.05; WMT, p < 0.05) compared to controls over the whole observation period. A significantly better behavioral outcome was observed in animals treated with hypothermia which showed no differences from controls 3-4 days after injury (PR, OF, BB, BW, WMT, p > 0.05). Lesion induced mortality was reduced in cooled animals but overall mortality rates were not influenced by this therapeutic measure. Neuronal cell loss in the CA1-CA4 region (p < 0.05) was reduced and the lesion size smaller (21%/p > 0.05) in hypothermic animals. Magnetic resonance imaging revealed that the lesion was more pronounced in the cortical grey matter after normothermia, whereas hypothermic animals showed more subcortical brain lacerations. In conclusion, intraischemic hypothermia significantly improved the behavioral outcome, and decreased lesion-induced mortality and the size of the lesion after an epidural focal mass lesion.
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PMID:Moderate hypothermia improves neurobehavioral deficits after an epidural focal mass lesion in rodents. 1290 39


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