Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dextromethorphan (DM) has been observed to afford neuroprotection in a variety of in vitro and in vivo experimental models of CNS injury. We have evaluated the neuroprotective activity of DM following both transient (2 h) and permanent focal cerebral ischemia in the rat. Middle cerebral artery occlusion (MCAO) was produced in male Sprague-Dawley rats using the intraluminal filament technique. Animals were dosed s.c with 20 mg/kg DM at 0.5, 1, 2, 4, and 6 hours post occlusion. Analysis of brain injury was performed 24 hours after permanent occlusion or reperfusion. Following transient MCAO, vehicle treated rats exhibited a total infarct volume of 203 +/- 33 mm3. DM produced a 61% reduction in infarct volume to 79 +/- 13 mm3. Permanent MCAO produced a larger infarct volume (406 +/- 44 mm3) which was not significantly reduced in size by treatment with DM (313 +/- 58 mm3). Infarcted hemispheric oedema was not different in vehicle treated rats following transient or permanent MCAO and was not reduced by DM in either group. Following transient MCAO, rectal temperature was elevated 1,2 and 5 hours post occlusion. While not inducing hypothermia or altering physiological parameters such as blood pressure and blood gases, DM attenuated this injury-related increase in temperature, an effect which appeared to correlate with its ability to protect neurons in temperature regulating hypothalamic centres. The DM-induced reduction in infarction demonstrated in our model of transient focal cerebral ischemia provides further support for the in vivo neuroprotective activity of this compound. Importantly, these data demonstrate the limited neuroprotective efficacy of DM when attempting to combat more severe focal ischemic injuries and imply that drug-induced hypothermia is not ultimately responsible for its protective action.
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PMID:Dextromethorphan protects against cerebral injury following transient, but not permanent, focal ischemia in rats. 915 Apr 12

Pericytes are essential components of the blood-brain barrier together with endothelial cells and astrocytes. Any disturbance of brain perfusion may result in blood-brain barrier dysfunction due to pericyte migration from the microvascular wall. The neuroprotective influence of hypothermia on ischemic brain injury has been clearly shown in models of both global and focal ischemia. Leakage of plasma proteins contributes to the extension of neuronal injury and hypothermia has a neuroprotective influence during the ischemic insult. This line of thinking impelled us to investigate the possible role of the pericytes in the occurrence of hypothermic protection during cerebral ischemia. In this study, we examined at the ultrastructural level the effect of moderate hypothermia on microvascular pericyte responses using a rat model of permanent middle cerebral artery occlusion. Twenty rats were divided into four groups. Middle cerebral artery occlusion was performed in all rats except the control group (first group), which was used to determine the pericyte morphology under normal conditions. In the second group, pericyte response to irreversible ischemia under normothermic conditions was examined at the end of the first hour. In the third group, pericyte response to hypoxia was examined under normothermic conditions three hours after ischemia. In the fourth group, temporalis muscle temperature was maintained at 27-29 degrees C for 1h after middle cerebral artery occlusion and pericyte response was then examined at the ultrastructural level. In ischemic normothermic conditions at the end of the first hour (Group 2), a separation was observed between pericytes and the basement membrane and this was interpreted as pericyte migration from the microvascular wall. In ischemic normothermic conditions at the end of the third hour (Group 3), basement membrane disorganization and increased space between the basement membranes were seen in addition to the differentiation of second group. In ischemic hypothermic conditions at the end of the first hour (Group 4), pericyte separation or migration from basement membrane were not seen and the blood-brain barrier remained firm. These findings were interpreted by the authors as a possible relationship between pericyte behavior and neural protection during hypothermia. We suggest that hypothermia may delay the pericyte response but not necessarily attenuate it, and should be associated with hypothermic protection.
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PMID:The effect of moderate hypothermia in acute ischemic stroke on pericyte migration: an ultrastructural study. 1792 22

Reperfusion injury is a complication of recanalization therapies after focal cerebral ischemia. The disruption of the blood-brain barrier (BBB) caused by up-regulated metalloproteinases (MMPs) can lead to edema and hemorrhage. Middle cerebral artery occlusion (MCAO=90 min) and reperfusion (R=24 h vs. 5 days) was induced in male Wistar rats. Rats were randomized in four groups: (1) control (C), (2) twice daily minocycline (30 mg/kg bodyweight) every day (M), (3) hypothermia (33 degrees C) for 4 h starting 60 min after occlusion (H), (4) combination of groups 2 and 3 (MH). Serial MRI was performed regarding infarct evolution and BBB disruption, MMP-2 and MMP-9 were assessed by zymography of serum and ischemic brain tissue, and a functional neuroscore was done at 24 h and 5 days. M and H reduced both infarct sizes, volume and signal intensity of BBB breakdown and improved neuroscore at all points in time to the same extent. This was most likely due to inhibition of MMP-2 and MMP-9. The presence of MMP-9 at 24 h or MMP-2 at 5 days in brain tissue correlated with BBB breakdown whereas serum MMP-2- and -9 showed no relationship with BBB breakdown. The combination MH had a small but not significantly additional effect over the single treatments. Minocycline seems to be as neuroprotective as hypothermia in the acute and subacute phase after cerebral ischemia. One essential mechanism is the inhibition of MMPs. The combination therapy is only slightly superior. The net effect of MMPs inhibition up to 5 days after focal cerebral ischemia is still beneficial.
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PMID:Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase. 1803 17

The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83; p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/-0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group 3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/-0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.
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PMID:Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats. 2003 28