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

Brain injury secondary to hypoxic-ischemic disease is the predominant form of all brain injury encountered in the perinatal period. The focus of this article is the most recent research developments in this field and especially those developments that should lead to the most profound effects on interventions in the first years of the new millennium. Neuronal injury is the predominant form of cellular injury in the term infant. The principal mechanisms leading to neuronal death after hypoxia-ischemia/reperfusion are initiated by energy depletion, accumulation of extracellular glutamate, and activation of glutamate receptors. The cascade of events that follows involves accumulation of cytosolic calcium and activation of a variety of calcium-mediated deleterious events. Notably this deleterious cascade, which evolves over many hours, may be interrupted even if interventions are instituted after termination of the insult, an important clinical point. Of the potential interventions, the leading candidates for application to the human infant in the relative short-term are mild hypothermia, inhibitors of free radical production, and free radical scavengers. Promising clinical data are available for the use of mild hypothermia.
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PMID:Perinatal brain injury: from pathogenesis to neuroprotection. 1124 83

Although accumulating evidence suggests that increased extracellular glutamate concentrations may play an important role in hypoxic-ischemic brain injury, dopamine and other catecholamines also seem to be involved. The N-methyl-D-aspartate receptor antagonist MK 801 and moderate hypothermia (32-34 degrees C) are each known to be neuroprotective, but their combined effect on the release and metabolism of neurotransmitters is unknown. Seven-day-old pups (n: 150) underwent right common carotid artery ligation to induce hemispheric ischemia, and were later subjected to 120 minutes of hypoxia with 8% O2 and 92% N2O. Half the rats (Group I, n: 74) were subjected to normothermic conditions throughout the hypoxic period. Moderate hypothermia (30-32 degrees C) was induced in the other pups (Group II, n: 76) immediately after artery occlusion, and was maintained throughout the hypoxic period. Prior to inducing hypoxia, half of the rats in each group (Groups IA and IIA) received vehicle solution (0.9% NaCI) and the other rats (Groups IB and IIB) received MK 801 (0.5 mg/kg) subcutaneously at 45 and 120 minutes after occlusion. Intracerebral temperature was recorded every 15 minutes after occlusion. Infarct area (n: 40) was calculated after staining with 2% 2,3,5 triphenyltetrazolium chloride. Neuronal damage (n: 42) was assessed by quantifying CA1-CA3 neuronal loss at five hippocampal levels. The amount of damage to the monoamine system of the corpus striatum was determined based on the dopamine and 3,4 dihydroxyphenylacetic acid levels in the corpus striatum in both hemispheres (n: 46), as measured by high-pressure liquid chromatography and compared with normal control pups' values (n: 10). The normothermia/saline-treated pups had significantly larger infarct areas than the MK 801 only, hypothermia only, or MK 801/hypothermia combination groups. Neuropathological examination and striatal tissue monoamine data also confirmed marked neuronal damage in this group. Although MK 801 treatment alone resulted in significantly smaller infarct area and less tissue damage than was observed in the normothermia/saline-treated group, the moderate hypothermia and the MK 801/hypothermia combination treatment groups both exhibited better neuronal protection, especially in the corpus striatum. The rats that received combined treatment also had a significantly lower mortality rate.
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PMID:Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats. 1178 Jul 74

An asphyxial cardiac arrest rat model, originally developed for Sprague-Dawley rats, was transferred to a Wistar rat model. Several strain specific life support adjustments, i.e. ventilator settings, anaesthesia, and drug requirements, were necessary to stabilize the model for Wistar rats. Despite these arrangements numerous resuscitation related variables appeared different. Three groups were evaluated and compared: a temperature monitored Wistar group 1 (n=34), a temperature controlled Wistar group 2 (n=26) and a temperature controlled Sprague-Dawley group 3 (n=7). Overall, Wistar rats seem to have more sensitive cardio-circulatory system evidenced by a more rapid development of cardiac arrest (164 vs. 201 s), requiring higher adrenaline/epinephrine doses (10 vs. 5 microg/kg) and requiring more time for recovery after resuscitation (i.e. for return of blood pressure and blood gases). Without strict temperature control (as in groups 2+3 rats) group 1 rats went into spontaneous mild to moderate hypothermia during the first 24 h after restoration of spontaneous circulation (ROSC). Spontaneous hypothermia delayed the development of overall visible CA1 neuronal damage 24-48 h, but did not prevent it; therefore the model seemed to be suitable for future studies. Neuronal damages in the CA1 region in Wistar rats appeared to be more as shrunken cell bodies and pyknotic nuclei before resorption took place, whereas in Sprague-Dawley rats appeared in the same region.
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PMID:Strain specific differences in a cardio-pulmonary resuscitation rat model. 1200 23

According to prior evidence opioid and serotonin release by lower brain stem neurons may contribute to hemorrhage-induced sympathoinhibition (HISI). Here we seek direct evidence for the activation of opioidergic, GABAergic, or serotonergic neurons by severe hemorrhage in the medulla oblongata. Blood was withdrawn from awake rats (40-50% total volume) causing hypotension and profound initial bradycardia. Other rats received the vasodilator hydralazine, causing tachycardia and hypotension. Neuronal activation was gauged by the presence of Fos-immunoreactive (ir) nuclei after 2 h. Serotonergic, enkephalinergic, and GABAergic neurons were identified by the presence of a diagnostic enzyme or mRNA. Hemorrhaged rats had 30% fewer non-GABAergic Fos-ir neurons in the rostral ventrolateral medulla (RVLM) than hydralazine-treated rats, but they had six times more Fos-ir neurons within the subependymal parapyramidal nucleus (SEPPN). Fos-labeled SEPPN neurons were serotonergic (40-60%), GABAergic (31%), enkephalinergic (15%), or had mixed phenotypes. The data suggest that a reduced sympathoexcitatory drive from RVLM may contribute to HISI. SEPPN neuronal activation may also contribute to HISI or could mediate defensive thermoregulatory mechanisms triggered by hemorrhage-induced hypothermia.
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PMID:Decompensated hemorrhage activates serotonergic neurons in the subependymal parapyramidal region of the rat medulla. 1218 4

Yohimbine, an alpha(2)-adrenoceptor antagonist, has been reported to protect hypoxic myocardium and inhibit carrier-mediated norepinephrine (NE) release and reperfusion arrhythmias (ventricular fibrillation; VF) in normothermic ischemia. In heart surgery, mild hypothermic (tepid) cardioplegia has been reported to reduce metabolic demand and permit immediate recovery of cardiac function. Therefore, we determined the effect of yohimbine on NE release and reperfusion arrhythmias in isolated perfused guinea pig hearts of tepid temperature (32 degrees C) ischemia model. Stepwise increase of global ischemia period (20, 40, and 60 min) induced a progressive increase of NE release and duration of VF. Neuronal uptake 1 inhibitor desipramine (100 nM) and Na(+)-H(+) exchanger inhibitor 5-N-ethyl-N-isopropyl-amiloride (10 microM) decreased NE and VF in 60-min hypothermic ischemia. This indicated that NE release induced by protracted tepid ischemia was due to carrier-mediated release. Yohimbine (1 microM) markedly reduced NE release and VF (p < 0.01 versus control) and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine [UK 14,304 (UK); 10 microM], an alpha(2)-adrenoceptor agonist, increased NE release and VF (p < 0.01 versus control). Yohimbine (1 microM) prevented the potentiated effect of UK (10 microM) in hypothermia (p < 0.01 versus UK). Our findings indicate that presynaptic reduction of carrier-mediated NE release seems to be one of the most important factors controlling reperfusion arrhythmias, and alpha(2)-adrenoceptor blockade by yohimbine (1 microM) in tepid ischemia may contribute to effective myocardial protection in terms of NE release and reperfusion arrhythmia.
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PMID:Carrier-mediated norepinephrine release and reperfusion arrhythmias induced by protracted ischemia in isolated perfused guinea pig hearts: effect of presynaptic modulation by alpha(2)-adrenoceptor in mild hypothermic ischemia. 1238 51

Brief forebrain ischemia in rodents induces selective and delayed neuronal death, particularly of hippocampal CA1 pyramidal neurons. Neuronal death is preceded by down-regulation specific to CA1 of GluR2, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that limits Ca(2+) influx. This alteration is hypothesized to cause neurodegeneration by permitting a lethal influx of Ca(2+) and/or Zn(2+) through newly formed GluR2-lacking AMPA receptors. Two days of mild hypothermia induced 1 h after ischemia potently and lastingly protects against ischemic injury. We examined molecular mechanisms underlying hypothermia-induced neuroprotection. We report that hypothermia rescues most hippocampal CA1 neurons from ischemia-induced cell death and attenuates ischemia-induced down-regulation of mRNA encoding the AMPA receptor subunit GluR2. Ischemia induced a marked down-regulation of GluR2 mRNA and a small down-regulation of GluR1 mRNA in CA1 at 2 days, as assessed by quantitative in situ hybridization. The ischemia-induced changes in gene expression were cell-specific in that GluR2 was not significantly altered in CA3 or dentate gyrus. After ischemia treated by hypothermia GluR2 mRNA expression was modestly reduced at 2 days and exhibited complete recovery to control levels at 7 days. Hypothermia prevented ischemia induced changes in GluR1 mRNA expression. These findings suggest that intervention at the level of transcriptional regulation of the GluR2 gene may be a mechanism by which prolonged postischemic cooling rescues CA1 neurons otherwise "destined to die."
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PMID:Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia. 1260 9

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

We hypothesized that selective brain hypothermia (SBHT) decreases production of hydroxyl radicals (*OH) induced by hypoxia-ischemia (H-I) and reperfusion and attenuates neuronal damage in neonatal rat brain. Anesthetized 7-day-old rats were divided into a normothermia (NT) group (n=6) and a SBHT group (n=7) and subjected to 90-min H-I, followed by a 90-min recovery period. Brain temperature (BT) was regulated by a water-cooled metallic plate placed under the head. The BT of the SBHT group was set at 31.0+/-1.0 degrees C during the H-I and recovery period. Microdialysis and the salicylate-trapping method were used to detect *OH in the striatum. Neuronal damage was quantified by counting the surviving neurons at 120 hr after reperfusion. The NT group had significant increases in 2,3-dihydroxybenzoic acid (DHBA) (223+/-166%) and 2,5-DHBA (321+/-153%) above baseline levels. The increases in 2,3-DHBA (127+/-40%) and 2,5-DHBA (133+/-33%) were significantly lower (p < 0.01) in the SBHT group. The number of surviving neurons was decreased significantly in the NT group but not in the SBHT group. We conclude that SBHT reduces *OH production during H-I and reperfusion and has protective effects against neuronal damage.
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PMID:Selective brain hypothermia protects against hypoxic-ischemic injury in newborn rats by reducing hydroxyl radical production. 1497 Jul 51

We investigated (1) whether cerebral hypothermia during kainic acid (KA)-induced seizures was neuroprotective; and (2) whether nitric oxide (NO) production in the brain during seizures was altered by cerebral hypothermia in immature rabbits. Twelve female rabbits, aged 2 weeks, were anesthetized, paralyzed and mechanically ventilated. We continuously measured NO production in the brain by NO-selective electrode, cortical electroencephalogram (EEG), regional cerebral blood flow (rCBF) by laser Doppler flowmetry, rectal and cerebral temperatures and mean arterial blood pressure (MABP) during KA (12 mg/kg, i.v.)-induced seizures in the hypothermic group (n = 6; rectal temperature, 33 degrees C), and in the normothermic group (n = 6; rectal temperature, 37 degrees C). The normothermic group showed a gradual increase in NO generation in the brain, which was significantly inhibited in the hypothermic group. There were no significant differences in the increases in rCBF, MABP, arterial blood gases, blood glucose, or EEG abnormalities between the two groups. Neuronal damages in the hippocampus (CA3) were significantly lower in hypothermia than in normothermia. These results suggest that hypothermia attenuates NO production during drug-induced seizures and decreases hippocampal brain lesions in the immature rabbit brain. These results may help to explain the neuroprotective effects of hypothermia.
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PMID:Hypothermia during kainic acid-induced seizures reduces hippocampal lesions and cerebral nitric oxide production in immature rabbits. 1503 Sep 6

Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of 12 subunits (alpha2-alpha10 and beta2-beta4). alpha5 Subunits, expressed throughout the central nervous system (CNS) and the autonomic nervous system (ANS), possess unique pharmacological properties. The effects of oxotremorine (OXO) on autonomic functions and tremor were examined in mice lacking alpha5 nAChR subunits (alpha5-/-) and compared with those in wild-type (WT) control mice. The alpha5-/- mice showed significantly increased salivation and tremor responses to OXO. The hypothermia, bradycardia and defecation induced by OXO were of similar magnitudes in the two mouse strains. The enhanced OXO effects in alpha5-/- mice indicate inhibitory effects of alpha5 subunits in autonomic ganglia, and support the participation of these subunits in cholinergic transmission in autonomic ganglia.
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PMID:Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced salivation and tremor. 1524 Feb 1


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