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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

The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia appears to be a general response of the CNS to many types of toxic insult. The organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to increase the production of GFAP as a consequence of widespread neuronal destruction. TMT also leads to transient reductions in body temperature (Tb), a response which may alter the neurotoxic effects of this compound. To study the role of Tb in the neurotoxic effects of TMT, rats were injected (i.v.) with saline or 8.0 mg/kg TMT and maintained at ambient temperatures (Ta) of 16, 22, or 30 degrees C for 72 hr while Tb (core) was measured periodically. Animals were then housed at a Ta of 22 degrees C for 35 days after which time their brains were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease in Tb of rats housed at 22 degrees C measured 3 hr after treatment. Tb of rats maintained at Ta's of 16 and 30 degrees C was unaffected by TMT initially (i.e., no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30 degrees C had a significantly elevated Tb. TMT led to marked elevations in GFAP levels, a response that was affected by Ta. In the hippocampus the elevation in GFAP was significantly greater in rats housed at 16 and 30 degrees C. A similar pattern was seen in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation. 756 91

In the companion paper we demonstrated that d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA) and d-methylenedioxymethamephetamine (d-MDMA), but not d-fenfluramine (d-FEN), appear to damage dopaminergic projections to the striatum of the mouse. An elevation in core temperature also was associated with exposure to d-METH, d-MDA and d-MDMA, whereas exposure to d-FEN lowered core temperature. Given these findings, we examined the effects of temperature on substituted amphetamine (AMP)-induced neurotoxicity in the C57BL/6J mouse. Levels of striatal dopamine (DA) and glial fibrillary acidic protein (GFAP) were taken as indicators of neurotoxicity. Alterations in ambient temperature, pretreatment with drugs reported to cause hypothermia in the mouse and hypothermia induced by restraint stress were used to affect AMP-induced neurotoxicity. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg) or d-MDMA (20 mg/kg) every 2 hr for a total of four s.c. injections. All three AMPs increased core temperature and caused large (> 75%) decreases in striatal dopamine and large (> 300%) increases in striatal glial fibrillary acidic protein 72 hr after the last injection. Lowering ambient temperature from 22 degrees C to 15 degrees C blocked (d-MDA and d-MDMA) or severely attenuated (d-METH) these effects. Pretreatment with MK-801 lowered core temperature and blocked AMP-induced neurotoxicity; elevation of ambient temperature during this regimen elevated core temperature and markedly attenuated the neuroprotective effects of MK-801. Pretreatment with MK-801 also lowered core temperature in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice but did not block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse. 807 68

Amphetamines (AMPs) can cause long-term depletions in striatal dopamine (DA) and serotonin (5-HT), and these decrements are often accepted as prima facie evidence of AMP-induced damage to the dopaminergic and serotonergic projections to striatum. Rarely are indices linked to neural damage used to evaluate the neurotoxicity of the AMPs. Here, we determined the potential neurotoxic effects of two substituted AMPs, d-methylenedioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in group-housed female C57BL6/J mice. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was the main indicator of d-MDMA-induced neural damage. Assays of tyrosine hydroxylase (TH), DA, and 5-HT were used to determine effects on DA and 5-HT systems. Since AMPs are noted for both their stimulatory and hyperthermia-inducing properties, activity, as well as core temperature, was monitored in several experiments. To extend the generality of our findings, these same end points were examined in singly housed female C57bL6/J mice and in group-housed male C57BL6/J or female B6C3F1 mice after treatment with d-MDMA. Mice received either d-MDMA (20 mg/kg) (singly housed mice received dosages of 20, 30, or 40 mg/kg) or d-FEN (25 mg/kg) every 2 h for a total of four sc injections. d-MDMA caused hyperthermia, whereas d-FEN induced hypothermia. d-MDMA cause a large (300%) increase in striatal GFAP that resolved by 3 wk and a 50-75% decrease in TH and DA that was still apparent at 3 wk, d-FEN did not affect any parameters in striatum. d-MDMA is a striatal dopaminergic neurotoxicant in both male and female C57BL6/mice, as evidenced by astrogliosis and depletions of DA in this area in both sexes. The greater lethality to males suggests they may be more sensitive, at least to the general toxicity of d-MDMA, that females. d-MDMA (20 mg/kg) induced the same degree of damage whether mice were housed singly or in groups. Higher dosages in singly housed mice induced greater lethality, but not greater neurotoxicity. d-MDMA was also effective in inducing striatal damage in mice of the B6C3F1 strain. Significant increases in activity were induced by d-MDMA, and these increases were not blocked by pretreatment with MK-801, despite the profound lowering of body temperature induced by this combination. A lowering of body temperature, whether by a 15 degree C ambient temperature (approx 2 degree drop), pretreatment with MK-801 (1.0 mg/kg prior to the first and third d-MDMA injections; approx 5-6 degrees C drop) or restraint (approx 5-6 degrees C drop) was effective in blocking the neurotoxicity of d-MDMA in both C57BL6/J and B6C3F1. The stimulatory effects of d-MDMA appeared to have little impact on the neurotoxicity induced by d-MDMA or the protection conferred by MK-801. These data suggest that in the mouse, the neurotoxic effects of d-MDMA, and most likly other AMPs, are linked to an effect on body temperature.
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PMID:The role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. 856 61

Early outcome measures of experimental traumatic brain injury (TBI) are useful for characterizing the traumatic severity as well as for clarifying the pathomechanisms underlying patterns of neuronal vulnerability. However, it is increasingly apparent that acute outcome measures may not always be accurate predictors of chronic outcome, particularly when assessing the efficacy of potential therapeutic regimens. This study examined the chronic histopathological outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post-traumatic brain hypothermia, a protocol that provides acute neuronal protection. Animals received a moderate parasagittal percussive head injury (2.01-2.38 atm) or sham procedure followed immediately by 3 h of brain hypothermia (30 degrees C) or normothermia (37 degrees C). Eight weeks following TBI, serial tissue sections were stained with hematoxylin and eosin or immunostained for glial fibrillary acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral to the injury site. Within the thalamus, focal necrosis was restricted to selective thalamic nuclei. Significant hippocampal cell loss was found in the ipsilateral dentate hilar region of both TBI groups. Quantitative volume measurements revealed significant decreases in cortical, thalamic and hippocampal volume ipsilateral to the impact in both TBI groups. Lateral ventricles were substantially enlarged in the TBI-normothermia group, an effect which was significantly attenuated by post-TBI hypothermia. The attenuation of lateral ventricular dilation by post-traumatic hypothermia is indicative of chronic neuroprotection in this TBI model. These data provide new information concerning the chronic histopathological consequence of experimental TBI and the relevance of this trauma model to chronic human head injury.
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PMID:Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. 903 68

This study investigated the effect of intra-ischemic hypothermia on astroglial reactions in the hippocampus following cerebral ischemia. Mongolian gerbils were subjected to forebrain ischemia by bilateral carotid occlusion of 10 min at a) 30 degrees C and b) 37 degrees C followed by normothermic reperfusion ranging from 1 to 3 days (d). The astrocytes were visualized by immunostaining against glial fibrillary acidic protein (GFAP), and neuronal injury was evaluated by using hematoxylin-eosin staining. In normothermic brains, reactive astrocytosis was noted in 1 and 2 d postischemic animals, becoming prominent in the 3 d postischemic group. Intense GFAP-positive cells with thickened processes were noted in all regions of the hippocampus, especially the CA1 region. These cells were seen to have migrated toward the stratum pyramidale which was normally devoid of such staining. Hypothermia significantly inhibited the GFAP-upregulation seen 3 d after normothermic ischemia. There was no significant neuronal damage in the 3 d hypothermic ischemic group. Since glial cell activation, as evidenced by GFAP-upregulation, precedes as well as accompanies neuronal damage, and since hypothermia, known to be neuroprotective, inhibits glial cell activation in the 3 d postischemic brain, it appears that glial cells play critical roles in neuronal survival or death following ischemia.
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PMID:GFAP-immunoreactivity following hypothermic forebrain ischemia. 910 35

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

Previous studies from our group have demonstrated an upregulation in nerve growth factor (NGF) RNA and protein in the cortex 24 h following traumatic brain injury (TBI) in a rat model. This increase in NGF is suppressed if rats are subjected to 4 h of whole-body hypothermia following TBI. In the present study we used in situ hybridization to extend our initial RNA gel-blot (Northern) hybridization findings by demonstrating that NGF RNA is increased in the cortex following TBI and that hypothermia diminishes this response. Further, by combining in situ hybridization with immunocytochemistry for glial fibrillary acidic protein we demonstrate that astrocytes are the major cellular source for the upregulation in NGF and that this upregulation can be observed in the hippocampus as early as 3 h posttrauma. The predominantly astrocytic origin suggests that the NGF upregulation is not related primarily to cholinotrophic activities. We hypothesize that its function is to stimulate upregulation of antioxidant enzymes, as part of an injury-induced cascade, and that supplementation of NGF or antioxidants may be warranted in hypothermic therapies for head injury.
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PMID:Astrocytes are the major source of nerve growth factor upregulation following traumatic brain injury in the rat. 950 Sep 53

Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure as a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammonia by the brain is the major cause of the central nervous system complications of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentrations or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT-1) and glutamate (GLT-1) transporters, the astrocytic structural protein glial fibrillary acidic protein (GFAP) the "peripheral-type" benzodiazepine receptor (PTBR) and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate in acute liver failure. Experimental acute liver failure also results in post-translational modifications of the serotonin and noradrenaline transporters resulting in increased extracellular concentrations of these monoamines. Therapeutic measures currently used to prevent and treat brain edema and encephalopathy in patients with acute liver failure include mild hypothermia and the ammonia-lowering agent L-ornithine-L-aspartate.
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PMID:Alterations in expression of genes coding for key astrocytic proteins in acute liver failure. 1174 25

The present study attempted to ascertain whether hypothermia attenuated the heat stroke-induced dopamine overload and gliosis in rat brain. Urethane-anesthetized rats were exposed to water blanket temperature (T(blanket)) of 42 degrees C until mean arterial pressure (MAP) began to decrease from their peak levels, which was arbitrarily defined as the onset of heat stroke. Extracellular concentrations of dopamine in brain were assessed by microdialysis methods. Hypothermia was accomplished by decreasing T(blanket) from 42 to 16 degrees C. The animals exposed to T(blanket) of 26 degrees C served as the normothermic controls. The values of MAP in heat stroke rats without hypothermia were all significantly lower than those in normothermic controls. However, the extracellular levels of dopamine and the number of glial fibrillary acidic protein-reactive cells in brain were greater. Hypothermia immediately after the onset of heat stroke reduced the heat stroke-induced circulatory shock as well as dopamine overload and gliosis in brain. The data demonstrate that hypothermia attenuates both dopamine overload and gliosis in rat brain associated with heatstroke.
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PMID:Hypothermia attenuates cerebral dopamine overloading and gliosis in rats with heatstroke. 1249 89


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