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

We investigated the effect of 30 degrees C whole body hypothermia on neuronal injury, astroglial reactivity and intracellular pH in rats subjected to 15 min of forebrain ischemia. Experimental groups included: (1) normothermic ischemia (n = 8), ischemia induced under 37 degrees C body temperature, (2) hypothermic ischemia (n = 6), ischemia induced under 30 degrees C body temperature. Cerebral intracellular pH was measured using in vivo 31P NMR spectroscopy over 7 days. Neuronal injury and astrocytic reactivity were evaluated using hematoxylin and eosin staining, and immunoreactivity to glial fibrillary acidic protein, respectively. Normothermic animals revealed significant alkalosis (P less than 0.01) at 48 h after ischemia compared to the pre-ischemic value. No significant intracellular pH change was detected after ischemia in the hypothermic group. Ischemic neuronal injury was prevented in the hypothermic animals, compared to the severe neuronal injury found in the normothermic animals (P less than 0.01). The marked astrocytosis of normothermic animals was significantly inhibited in the hypothermic animals (P less than 0.01). Our data indicate, that hypothermia significantly inhibits neuronal injury as well as post-ischemic alkaloids and astrocytosis, induced by 15 min of forebrain ischemia in the rat.
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PMID:Neuronal damage, glial response and cerebral metabolism after hypothermic forebrain ischemia in the rat. 138 61

It has been proposed that lithium ion desensitizes neuronal receptors that function via the inositol phospholipid signaling mechanism. We examined the effects of lithium chloride on the morphologic outcome after 5 minutes of cerebral ischemia induced in gerbils by occluding both common carotid arteries under brief halothane anesthesia. In three treated groups of 10 gerbils each, 5 meq/kg i.p. lithium chloride was given 2 days, 1 day, and 2 hours before ischemia; 2 hours before ischemia; or immediately after the end of ischemia. Corresponding control groups of nine or 10 gerbils each received equivalent volumes of saline injected at comparable times. All gerbils were perfusion-fixed 1 week later, and neuronal density of the hippocampal CA1 pyramidal cells was determined. Lithium induced very mild intraischemic systemic hypothermia, but postischemic hyperthermia developed in both treated and control groups. Neuronal densities were equal in corresponding groups. The results indicate that our regimen of lithium administration provides no benefit in survival of hippocampal neurons, and intraischemic hypothermia of less than 0.8 degrees C is not protective. Other strategies to inactivate the signal transduction system that is specific for excitatory neurotransmission should be evaluated.
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PMID:Lithium ion does not protect brain against transient ischemia in gerbils. 184 49

In vitro ischemia models have utilized oxygen, or oxygen and glucose deprivation to simulate ischemic neuronal injury. Combined oxygen and glucose deprivation can induce neuronal damage which is in part mediated through NMDA receptors. Severe oxygen deprivation alone however can cause neuronal injury which is not NMDA mediated. We tested the hypothesis that NMDA, or non-NMDA receptor mediated mechanisms may predominate, to induce neuronal injury following severe oxygen deprivation depending on the presence of glucose. We found that NMDA receptor blockade using dizocilpine (MK-801), DL-2-amino-5-phosphonovaleric acid (APV), or CGS 19755, was highly effective in reducing CA1 injury in organotypic hippocampal cultures, caused by complete oxygen and glucose deprivation. Complete oxygen deprivation alone however, caused CA1 neuronal injury which was not diminished using NMDA receptor blockade alone with MK-801 or APV, or in combination with AMPA/kainate receptor blockade using 6-cyano-7-dinitroquinoxalone-2,3-dione (CNQX). Neuronal protective strategies which act primarily through non-glutamate dependent mechanisms, including hypothermia, low chloride and calcium, and the free radical scavenger, alpha-phenyl-tert-butyl nitrone (PBN), provided neuronal protection against complete oxygen, as well as combined oxygen/glucose deprivation. Raising the pH using Hepes buffer during complete oxygen deprivation did not result in neuronal protection by NMDA receptor blockade. Partial oxygen deprivation alone, partial oxygen deprivation combined with glucose deprivation, glucose deprivation alone, and also glutamate exposure, all produced neuronal damage that was reduced by NMDA receptor blockade. The presence of glucose during complete oxygen deprivation appears to prevent glutamate receptor blockade from reducing neuronal injury in organotypic hippocampal cultures.
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PMID:Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures. 747 21

Cerebral protection combines techniques aimed 1) to avoid death of neurones which sustained primary ischemic of traumatic insults and 2) to prevent secondary insults to the brain. The chemical brain retractor concept includes the use of a total intravenous anesthesia technique, mild hypocapnia and mannitol with strict monitoring and maintenance of the global cerebral homeostasis. This contributes to decrease brain volume and intracranial pressure and allows the best possible access to the operating site, while avoiding excessive pressure under the surgical brain retractors. Neuronal protection is based on a better understanding of the biological basis of secondary brain damage; therapeutic or prophylactic techniques include the use of specific pharmacological agents, hypothermia, hemodilution and maintenance of an elevated cerebral perfusion pressure. In short, although the favourable effects of such techniques are nor easy to demonstrate in man, their use in today's clinical practice, in association with the concept of the chemical brain retractor, is an effective way to prevent ischemic cerebral insults during neurosurgical procedures.
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PMID:[Relaxation and protection of the brain on the operating table]. 759 56

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

Neuronal degeneration after trauma is mediated in part by release of excitatory amino acids (EAAs) and oxygen free radicals (OFR). We evaluated the effect of i.v. treatment with a hydroxyl radical scavenger ((+/-)-N,N'-propylenedinicotinamide; AVS) and spinal hypothermia (33 degrees C) on spinal CSF glutamate release after spinal trauma. In a control group, spinal compression evoked at 10 min a significant increase (5-fold) in glutamate which declined over 4 h (2.1-fold). AVS treatment attenuated glutamate release but had no additive effect. These data suggest that this compound can be effective in modulating spinal excitotoxicity resulting from increased OFR synthesis and corresponding potentiation of EAA release.
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PMID:The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal injury in rats. 963 82

Despite the enormous scientific efforts that have been made to clarify the pathophysiology of ischemic neuronal injury, the mechanism responsible for neuronal cell death after ischemia remains unclear. Neuronal injury can be roughly classified into three categories: acute ischemic injury, delayed neuronal death and neuronal injury in the penumbra. Flow disturbance known as the noreflow phenomenon and postischemic hypoperfusion is the first limiting factor for neuronal resuscitation after an ischemic insult. Extracorporeal circulation has been tried in an attempt to prevent this blood flow disturbance, but it has become apparent that this is no more effective than conventional resuscitation. Delayed neuronal death seems to be triggered by short exposure to ischemia. Although a molecular mechanism including "glutamate excitotoxicity" has been proposed to explain this phenomenon, the details are still uncertain. The interventional point underlying the protective effect of hypothermia against delayed neuronal death may be the key to understanding its pathophysiology. Neuronal death in the penumbra seems to show deterioration through a mechanism of repeated depolarization "spreading depression", although spreading depression itself has no harmful effect on neurons. The pathophysiological mechanism of spreading depression in combination with flow restriction and other relevant factors related to ischemia remains to be investigated.
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PMID:[The pathophysiology of ischemic neuronal injury: an overview]. 969 85

Choreoathetosis, seizures, and impaired mental development continue to occur in children undergoing cardiopulmonary bypass (CPB) and profound hypothermia with or without circulatory arrest. Although there is some evidence that the hypothermia itself may be causing these neurologic problems, skepticism remains because of lack of evidence from experimental studies simulating the clinical setting. In this experimental study, we examined the effect of profound and moderate hypothermia on the brain while maintaining normal flow rates during CPB. Ten adult mongrel dogs equally divided into two groups were anesthetized and subjected to CPB and varying levels of hypothermia (group 1, < or = 15 degreesC; group 2, < or = 2 degreesC). Both groups were kept at the desired temperature for 1 hour prior to rewarming and discontinuation of CPB. The dogs were euthanized 4-6 weeks later and neuropathologic studies were performed. The mean CPB flow rates during cooling and at the desired rectal temperature were comparable in both groups: group 1, 108 +/- 10 ml/kg/min versus 106 +/- 7 ml/kg/min in group 2 (p = NS) and 95 +/- 12 ml/kg/min in group 1 versus 101 +/- 5 ml/kg/min in group 2 (p = NS). Because of the difference in temperature between the two groups, the mean cooling time (onset of CPB to desired rectal temperature) was longer in group 1 (70 +/- 14 minutes) than in group 2 (28 +/- 11 minutes, p = 0.007). Hence, the total mean CPB time was also longer in group 1 (198 +/- 25 minutes) than in group 2 (143 +/- 13 minutes, p = 0.002). The lowest mean blood and rectal temperature achieved in group 1 were 11 +/- .9 degreesC and 12 +/- 1 degreesC versus 29 +/- .4 degreesC (p < 0.001) and 30 +/- .6 degreesC (p = 0.001), respectively, in group 2 (p = 0.001). Neuronal loss and degeneration was noted in all dogs in group 1 ranging from 2 to 8 cells per 1000 cells counted compared to none in group 2 (p = 0.05). These lesions occurred in both the basal ganglia and the cortex, although they were more marked in the caudate when compared to the cortex and cerebellum. Both in the cortex and in the caudate, neuronal loss was more marked around the capillaries. We conclude that the use of profound hypothermia of < or =15 degreesC and maintenance of normal flow rates during cooling at this temperature for 1 hour produces neuronal loss and degeneration in the brain. These lesions being more marked around capillaries points to the vulnerability of the neurons, probably because of their high lipid content to injury from the cold perfusate.
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PMID:Experimental evidence of cerebral injury from profound hypothermia during cardiopulmonary bypass. 970 64

This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.
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PMID:Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis. 1049

Neuronal nicotinic receptors are ligand-gated ion channels of the central and peripheral central nervous system that regulate synaptic activity from both pre- and postsynaptic sites. The present study establishes the acute interaction of bupropion, an antidepressant agent that is also effective in nicotine dependence, with nicotine and nicotinic receptors using different in vivo and in vitro tests. Bupropion was found to block nicotine's antinociception (in two tests), motor effects, hypothermia, and convulsive effects with different potencies in the present investigation, suggesting that bupropion possesses some selectivity for neuronal nicotinic receptors underlying these various nicotinic effects. In addition, bupropion blocks nicotine activation of alpha(3)beta(2), alpha(4)beta(2), and alpha(7) neuronal acetylcholine nicotinic receptors (nAChRs) with some degree of selectivity. It was approximately 50 and 12 times more effective in blocking alpha(3)beta(2) and alpha(4)beta(2) than alpha(7.) This functional blockade was noncompetitive, because it was insurmountable by increasing concentration of ACh in the nAChRs subtypes tested. Furthermore, bupropion at high concentration failed to displace brain [(3)H]nicotine binding sites, a site largely composed of alpha(4)beta(2) subunit combination. Given the observation that bupropion inhibition of alpha(3)beta(2) and alpha(4)beta(2) receptors exhibits voltage-independence properties, bupropion may not be acting as an open channel blocker. These effects may explain in part bupropion's efficacy in nicotine dependence. Our present findings suggest that functional blockade of neuronal nAChRs are useful in nicotine dependence treatment.
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PMID:Bupropion is a nicotinic antagonist. 1099 97


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