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

Mild hypothermia reduces secondary damage after traumatic brain injury (TBI) in rodent models; however, the mechanisms involved in this beneficial effect remain unclear. We previously reported that TBI induces the upregulation of adhesion molecules and infiltration of neutrophils (PMN) in brain. Since PMN accumulation may be associated with the development of hyperemia and blood-brain barrier injury, we hypothesized that hypothermia would reduce acute inflammation after TBI in rats. To test this hypothesis, rats were anesthetized and subjected to TBI by controlled cortical impact to left parietal cortex. Brain temperature was controlled at 32 degrees C, 37 degrees C, or 39 degrees C (n = 8 per group) for 4 h after TBI, then rats were sacrificed and brain were harvested. Immunohistochemistries were performed on brain sections using antibodies that recognize the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1), and PMN. PMN were also quantified using a myeloperoxidase (MPO) assay. PMN accumulation in injured brain was decreased in rats maintained at 32 degrees C vs 39 degrees C (4-fold by immunohistochemistry and 8-fold by MPO, p < 0.05). E-selectin was induced after TBI, but not attenuated by hypothermia. ICAM-1 was not up-regulated at this early time after TBI. Based on these preliminary data, we conclude that mild hypothermia reduces PMN accumulation in injured brain during the initial 4 h after TBI, without decreasing adhesion molecule expression.
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PMID:The relationship between brain temperature and neutrophil accumulation after traumatic brain injury in rats. 941 40

Ischemia and reperfusion causes tissue injury that can be partially prevented by mild hypothermia. In this study we postulated that hypothermic protection could occur if imposed only during reperfusion. Rabbit ears were partially amputated, the central artery occluded for 6 h followed by reperfusion at an ambient temperature of either 20 or 24 degrees C resulting in ischemic ear temperatures of 22.5 vs. 24.7 degrees C. Ear temperature of rabbits remaining in the 24 degrees C room increased with reperfusion to 32.4 degrees C whereas those moved to the 20 degrees C room increased to 30.0 degrees C by 2 h of reperfusion. Ear volume was used as a measure of tissue edema and was measured for 7 days after the ears were allowed to reperfuse. Normalized myeloperoxidase content (polymorphonuclear cell accumulation) was significantly greater in the 24 degrees C ischemia-24 degrees C reperfusion group compared with the other groups. Ear edema was significantly less in the two groups exposed to 20 degrees C reperfusion compared with the 24 degrees C ischemia-24 degrees C reperfusion group. Peak ear volume was 5.0 times baseline for the 24 degrees C ischemia-24 degrees C reperfusion, 4.0 times baseline for the 20 degrees C ischemia-24 degrees C reperfusion, 3.4 times baseline for the 24 degrees C ischemia-20 degrees C reperfusion, and 3.3 times baseline for the 20 degrees C ischemia-20 degrees C group. We conclude that mild hypothermia reduces PMN accumulation and is more effective in preventing tissue injury when imposed during reperfusion compared with during ischemia.
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PMID:Mild hypothermia during reperfusion reduces injury following ischemia of the rabbit ear. 948 56

The purpose of the present work was to evaluate the kallikrein-kinin system and effects of hypothermia during renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min ischemia for different periods of reperfusion. Our results demonstrate that short periods of ischemia followed by reperfusion did not cause significant alterations in kallikrein activity, Evans Blue (EB) extravasation, prokallikreins, myeloperoxidase activity or plasma creatinine concentration. Edema was evident at 1 h reperfusion in the treated mice, but returned to basal values after 24 h reperfusion. Kallikrein activities and EB extravasation showed a significant increase in 60 min ischemic mice. Myeloperoxidase activity in the kidney of the mice confirmed net infiltration in the group with 60 min ischemia and 24 h reperfusion. The generation of kinins and activation of matrix degrading enzymes by tissue kallikrein, liberated from both renal and infiltrated leukocytes, could be responsible at least in part for the damage observed in the kidney of mice subject to 60 min ischemia and reperfusion. The hypothermia significantly reduced the inflammatory process in the 60 min ischemic mice, and did prevent an increase in vascular permeability. Nevertheless, the tissue edema was not shown to change between normothermic and hypothermic ischemic mice.
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PMID:Renal ischemia-induced increase in vascular permeability is limited by hypothermia. 1059 59

The purpose of this study was to investigate: 1) the temporal and regional profile of polymorphonuclear leukocyte (PMNL) infiltration after moderate traumatic brain injury using the parasagittal fluid percussion model and 2) the effects of posttraumatic hypothermia (30 degrees C) and hyperthermia (39 degrees C) on the acute and subacute inflammatory response. We hypothesized that posttraumatic hypothermia would reduce the degree of PMNL accumulation whereas hyperthermia would exacerbate this response to injury. In the first series of experiments we quantitated the temporal profile of altered myeloperoxidase activity under normothermic (37 degrees C) conditions (n = 20). The rats were allowed to survive for 3 hours, 24 hours, 3 days, or 7 days after trauma, and brains were dissected into cortical and subcortical regions ipsilateral and contralateral to injury. Additional animals were perfused and fixed for the immunocytochemical visualization of myeloperoxidase (n = 15). In the second series of experiments, rats (n = 25) were killed 3 hours or 3 days after the 3-hour monitoring period of normothermia (36.5 degrees C), hypothermia (30 degrees C), or hyperthermia (39 degrees C) (n = 4 to 5 per group), and myeloperoxidase activity was again quantitated. In normothermic rats, the enzymatic activity of myeloperoxidase was significantly increased (P < 0.05) at 3 hours within the anterior cortical segment (213.97 +/- 56.2 versus control 65.5 +/- 52.3 U/g of wet tissue; mean +/- SD) and posterior (injured) cortical and subcortical segments compared to sham-operated rats (305.76 +/- 27.8 and 258.67 +/- 101.4 U/g of wet tissue versus control 62.8 +/- 24.8 and 37.28 +/- 35.6 U/g of wet tissue; P < 0.0001, P < 0.05, respectively). At 24 hours and 7-days after trauma only the posterior cortical region (P < 0.005, P < 0.05, respectively) exhibited increased myeloperoxidase activity. However, 3 days after trauma, myeloperoxidase activity was also significantly increased within the anterior cortical segment (P < 0.05) and in posterior cortical and subcortical regions compared to sham-operated cortex (P < 0.0001, P < 0.05, respectively). Immunocytochemical analysis of myeloperoxidase reactivity at 3 hours, 24 hours, 3- and 7-days demonstrated large numbers of immunoreactive leukocytes within and associated with blood vessels, damaged tissues, and subarachnoid spaces. Posttraumatic hypothermia and hyperthermia had significant effects on myeloperoxidase activity at both 3 hours and 3 days after traumatic brain injury. Posttraumatic hypothermia reduced myeloperoxidase activity in the injured and noninjured cortical and subcortical segments compared to normothermic values (P < 0.05). In contrast, posttraumatic hyperthermia significantly elevated myeloperoxidase activity in the posterior cortical region compared to normothermic values at both 3 hours and 3 days (473.5 +/- 258.4 and 100.11 +/- 27.58 U/g of wet tissue, respectively, P < 0.05 versus controls). These results indicate that posttraumatic hypothermia decreases early and more prolonged myeloperoxidase activation whereas hyperthermia increases myeloperoxidase activity. Temperature-dependent alterations in PMNL accumulation appear to be a potential mechanism by which posttraumatic temperature manipulations may influence traumatic outcome.
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PMID:Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies. 1072 18

The present study addresses the effects of moderate posttraumatic hypothermia (32 degrees C) on the temporal and regional profile of polymorphonuclear leukocyte (PMNL) accumulation after traumatic spinal cord injury (SCI). We hypothesized that posttraumatic hypothermia would reduce the degree of inflammation by reducing PMNL infiltration. Rats underwent moderate spinal cord injury at T10 using the NYU impactor device. In the first study, the temporal profile of myeloperoxidase (MPO) activity (a marker of neutrophil accumulation) under normothermic (37 degrees C) conditions was determined. The animals were allowed to survive for 3 or 24 h, or 3 or 7 days after SCI. Spinal cords were dissected into five segments rostral and caudal to the injury site. Additional animals were studied for the immunocytochemical visualization of MPO. In the second study, rats were sacrificed at 24 h after a monitoring period of normothermia (36.5 degrees C/3 h) or hypothermia (32.4 degrees C/3 h) with their controls. In the time course studies, MPO enzymatic activity was significantly increased at 3 and 24 h within the traumatized T10 segment compared to controls. MPO activity was also increased at 3 h within the rostral T8 and T9 segments and caudal T11 and T12 segments compared to controls. At 24 h after trauma, MPO activity remained elevated within both the rostral and caudal segments compared to control. By 3 days, the levels of MPO activity were reduced compared to the 24-h values but remained significantly different from control. Neutrophils that exhibited MPO immunoreactivity were seen at 6 and 24 h, with a higher number at 3 days. PMNLs were located within the white and gray matter of the lesion and both rostral and caudal to the injury site. Posttraumatic hypothermia reduced MPO activity at 24 h in the injured spinal cord segment, compared to normothermic values. The results of this study indicate that a potential mechanism by which hypothermia improves outcome following SCI is by attenuating posttraumatic inflammation.
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PMID:Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. 1077 15

Brain injury due to bacterial meningitis results in a high mortality rate and significant neurologic sequelae in survivors. The objective of this study was to determine if the application of moderate hypothermia shortly after the administration of antibiotics would attenuate the inflammatory response and increase in intracranial pressure that occurs in meningitis. For this study we used a rabbit model of severe Group B streptococcal meningitis. The first component of this study evaluated the effects of hypothermia on blood-brain barrier function and markers of inflammation in meningitic animals. The second part of the study evaluated the effects of hypothermia on intracranial pressure, cerebral perfusion pressure and brain edema. This study demonstrates that the use of hypothermia preserves CSF/serum glucose ratio, decreases CSF protein and nitric oxide and attenuates myeloperoxidase activity in brain tissue. In the second part of this study we show a decrease in intracranial pressure, an improvement in cerebral perfusion pressure and a decrease in cerebral edema in hypothermic meningitic animals. We conclude that in the treatment of severe bacterial meningitis, the application of moderate hypothermia initiated shortly after antibiotic therapy improves short-term physiologic measures associated with brain injury.
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PMID:Hypothermia as an adjunctive treatment for severe bacterial meningitis. 1103 98

Systemic hypothermia has been shown to exert neuroprotective effects in experimental ischemic CNS models caused by vascular occlusions. The present study addresses the question as to whether systemic hypothermia has similar neuroprotective qualities following severe spinal cord compression trauma using microtubule-associated protein 2 (MAP2) immunohistochemistry combined with the avidin-biotin-peroxidase complex method as marker to identify neuronal and dendritic lesions. Fifteen rats were randomized into three equally sized groups. One group sustained thoracic laminectomy, the others severe spinal cord compression trauma of the T8-9 segment. The control group contained laminectomized animals submitted to a hypothermic procedure in which the esophageal temperature was reduced from 38 degrees C to 30 degrees C. The two trauma groups were either submitted to the same hypothermic procedure or kept normothermic during the corresponding time. All animals were sacrificed 24 h following the surgical procedure. The MAP2 immunostaining in the normothermic trauma group indicated marked reductions in MAP2 antigen in the cranial and caudal peri-injury zones (T7 and T10, respectively). This reduction was much less pronounced in the hypothermic trauma group. In fact, the MAP2 antigen was present in almost equally sized areas in both the hypothermic groups independent of previous laminectomy alone or the addition of trauma. Our study thus indicates that hypothermia has a neuroprotective effect on dendrites of rat spinal cords subjected to compression trauma.
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PMID:Systemic hypothermia following spinal cord compression injury in the rat: an immunohistochemical study on MAP 2 with special reference to dendrite changes. 1104 77

Glutathione peroxidase (GPX)-1 and gastrointestinal (GI) epithelium-specific GPX (GPX-GI), encoded by Gpx1 and Gpx2, provide most GPX activity in GI epithelium. Although homozygous mice deficient in either the Gpx1 or Gpx2 gene appeared to be normal under standard housing conditions, homozygous mice deficient in both genes, double-knockout (KO) mice, had symptoms and pathology consistent with inflammatory bowel disease. These symptoms included a high incidence of perianal ulceration, growth retardation that started around weaning, and hypothermia that resembled that observed in calorie-restricted mice, even though the double-KO mice in our study were allowed to eat ad libitum. The growth retardation and hypothermia were components of cachexia, which is fatal in a high percentage of mice. Histological examination revealed that the double-KO mice had a high incidence of mucosal inflammation in the ileum and colon but not in the jejunum. Elevated levels of myeloperoxidase activity and lipid hydroperoxides were also detected in colon mucosa of these homozygous double-KO mice. These results suggest that GPX is essential for the prevention of the inflammatory response in intestinal mucosa.
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PMID:Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. 1151 97

Stress-induced change in the distribution of the drug pyridostigmine (PYR) has been proposed as a contributing factor to unexplained illnesses in Persian Gulf War veterans. We evaluated the effects of two stress models, forced running and forced swimming, on acute PYR (30 mg/kg, p.o.) toxicity and cholinesterase (ChE) inhibition in the blood and selected brain regions of young adult male Sprague-Dawley rats (6 weeks of age). Plasma corticosterone levels were measured at 0, 1 and 3 h after termination of forced swimming or forced running to confirm the induction of stress. PYR was given either immediately before stress (15 min swimming; 20 min running) or immediately after stress (15 min swimming; 90 min running) and cholinergic toxicity and ChE inhibition were evaluated at 1, 2 or 4 h after PYR exposure. Additionally, rats were subjected to either swimming (15 min) or running (90 min) stress, anesthetized, injected with horseradish peroxidase (HRP, 100 mg/kg, transcardial) and brain-regional HRP activity measured as an indicator of altered blood-brain barrier integrity. Both forced swimming and forced running resulted in significant elevations of plasma corticosterone levels. PYR caused cholinergic toxicity at all time-points evaluated. Swimming and running stress had little influence on expression of PYR-induced toxicity, however. Blood ChE activity was generally inhibited 77-91% at 1-4 h after PYR, but rats pretreated with PYR prior to forced swimming showed lesser inhibition (64%) 1 h after dosing, possibly because of swimming-induced hypothermia and delayed absorption of the drug. Minimal changes in ChE activity were noted in frontal cortex, cerebellum and hippocampus following PYR exposure (maximal inhibition 28%), and neither swimming nor running stress affected the degree of inhibition. Neither stress model increased HRP accumulation in any brain region. The results suggest that stress associated with forced running or forced swimming has little effect on acute PYR toxicity, entry of PYR into the brain or PYR-induced brain-regional ChE inhibition.
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PMID:Neither forced running nor forced swimming affect acute pyridostigmine toxicity or brain-regional cholinesterase inhibition in rats. 1206 28

Patients with intracerebral hemorrhage (ICH) may deteriorate progressively after the initial ictus because of the brain edema around the hematoma. Recently, thrombin has become known to play an important role in the brain edema formation after ICH. In this study, we examined the effect of brain hypothermia on brain edema formation after hematoma and thrombin injection into the brain in rats and clarified the mechanism of hypothermia on brain damage. Anesthetized Sprague-Dawley rats received an injection of 100 microL of autologous blood or 10 units of bovine thrombin into the basal ganglia. Animals were divided into the normothermic and hypothermic groups, which were housed in a room at 25 degrees C and in a cold room at 5 degrees C respectively, for 24 hours. Brain water content was significantly reduced with hypothermia in the cortex (80.8 vs. 79.7% p < 0.05) after hematoma induction. After thrombin injection, brain water content was also significantly reduced with hypothermia in the basal ganglia (84.5 vs. 82.2%; p < 0.01), accompanied by a significant reduction in blood-brain barrier (BBB) permeability to Evan's blue (29.4 vs. 11.6 ng/g tissue; p < 0.05) and in accumulation of polymorphonuclear leukocytes (3.03 vs. 0.27 U of myeloperoxidase/g tissue; p < 0.01). This study indicates that brain hypothermia significantly reduces brain edema formation after hematoma and thrombin injection into the brain in rats. Inhibition of thrombin-induced BBB breakdown and inflammatory response with hypothermia appear to contribute to brain protection in this model.
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PMID:Effects of brain hypothermia on brain edema formation after intracerebral hemorrhage in rats. 1216 13


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