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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behavior of the BBB in cerebral ischemia was studied in symptom-positive Mongolian gerbils subjected to left common carotid artery occlusion using Evans Blue dye as indicator of BBB injury. The BBB damage was demonstrable grossly by the presence of areas of blue discoloration, and microscopically by the presence of a bright red fluorescent tracer, localized mostly in the neurons. The survey of various groups of animals revealed a direct relationship between the incidence and time of appearance of the BBB lesions and the duration of the ischemic occlusion. This relationship can be interpreted as another example of the previously described "maturation" phenomenon. A relatively late occurrence of the BBB injury in cerebral ischemia, at the time when the affected brain tissue shows severe, edematous histopathologic changes indicates that the brain edema, as the main complication of ischemia, could be regarded as being primarily of the cytotoxic type.
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PMID:Experimental cerebral ischemia in Mongolian gerbils III. Behaviour of the blood-brain barrier. 125 83

Recent investigations have proposed that, after temporary ischemia, pentastarch may reduce microvascular permeability and reperfusion injury. However, this hypothesis has not been tested in the brain. Accordingly, after 180 min of temporary middle cerebral artery occlusion, the effect of pentastarch or albumin on blood-brain barrier permeability and cerebral injury was investigated in isoflurane-anesthetized rats. One of the following was maintained for the final 60 min of occlusion and throughout reperfusion: control-hematocrit was not manipulated; pentastarch-hematocrit was decreased to approximately 30% with pentastarch; or albumin-hematocrit was decreased (approximately 30%) with albumin. Part A (n = 21): 30 min of reperfusion was allowed, and blood-brain barrier permeability was determined with the indicator dye Evans Blue. Part B (n = 14): in different animals, 120 min of reperfusion was allowed, and cerebral injury (2,3,5-triphenyltetrazolium chloride stain) and edema (specific gravity) were assessed. Part C (n = 4): in different animals, the blood-brain barrier was evaluated by electron microscopy. Evans Blue (micrograms per gram brain tissue, mean +/- SD) was greater in the control (20.8 +/- 9.0) and albumin (15.5 +/- 7.3) groups versus the pentastarch (4.7 +/- 2.7) group (P less than 0.05). Brain injury (percent of hemisphere ipsilateral to occlusion) was less and specific gravity greater in the pentastarch (33 +/- 8 and 1.040 +/- 0.003 respectively) versus the albumin group (45 +/- 6 and 1.035 +/- 0.003). This study supports the hypothesis that during temporary cerebral ischemia, pentastarch decreases brain injury and edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Temporary cerebral ischemia. Effects of pentastarch or albumin on reperfusion injury. 137 71

The feline infusion model of brain edema was used to evaluate the role of bradykinin in the etiology and pathophysiology of vasogenic brain edema. Bradykinin (3 or 90 ug in 600 microL saline) did not alter normocapnic regional cerebral blood flow (rCBF) nor induce specific changes in either the somatosensory (SEP) or motor (MEP) evoked potentials. The mean increases in ICP (from 4.5 to 16.1 mmHg) and peri-infusion white matter water content (from 69.4 to 79.8 ml/100 g tissue), mean decrease in lumped craniospinal compliance (from 0.040 to 0.014 ml/mmHg) and local histological changes were all similar to those after 600 microL saline infusion. The interstitial bradykinin infusion caused focal blood-brain-barrier (BBB) opening to Evans Blue dye and was chemotaxic for granulocytes. After the infusion there was a global loss of rCBF CO2 reactivity but there was no ischemia at normocapnia. These results show that bradykinin in brain edema fluid, at concentrations greater than those found in neuropathological conditions, can open the BBB of normal cerebral parenchymal capillaries and cause vascular dysregulation. In neuropathological conditions bradykinin may therefore potentiate formation of vasogenic brain edema but does not contribute to perilesional brain dysfunction.
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PMID:The role of bradykinin in the etiology of vasogenic brain edema and perilesional brain dysfunction. 159 96

The influence of systemic blood pressure on blood-brain barrier leakage and hemorrhage in brain ischemia was evaluated in Sprague-Dawley rats with blood pressures at the lower and upper limit normally found in these animals when anesthetized on 70% N2O:30% O2. 24 h after unilateral cerebral microembolization - when significant increases in water content and barrier permeability and decrease in blood flow is present - the extravasation of Evans Blue-albumin and inulin as well as hemorrhage in the infarcted brain area was considerably more prominent in animals with the higher blood pressure. The findings imply that attempts to elevate pressure, as well as subacute surgical circulatory reconstruction to increase perfusion of an ischemic area, may be potentially harmful.
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PMID:Influence of blood pressure on blood-brain barrier function in brain ischemia. 650 45

The role of free oxygen radicals in blood-brain barrier (BBB) disruption and postischemic hyperemia was evaluated in the rabbit model of focal cerebral ischemia-reperfusion. Six groups of rabbits underwent clipping of the anterior cerebral, middle cerebral, and intracranial internal carotid arteries. Cerebral blood flow (CBF) was measured by using radiolabeled microspheres, before, during, and 15 minutes after 1-hour occlusion of these arteries. After 50 minutes of ischemia, Group 1 animals (control) received a placebo. Animals in Groups 2-4 received one of three drugs: catalase at 10 mg/kg, methimazole at 5 mg/kg, or indomethacin at 10 mg/kg. A fifth group received a tungsten-supplemented diet for 14 days before ischemia was induced, and a sixth group was sham operated. Microvascular integrity within the brain was determined by the presence or absence of Evan's Blue (EB)-albumin dye leakage across the BBB and was measured by microspectrofluorometry. In the control group during ischemia, CBF dropped to 14%, 7%, and 11% of preischemic levels in rostral, middle, and caudal sections of the brain, respectively, as characterized by extensive EB-albumin dye leakage through the BBB into the ischemic hemisphere. During early reperfusion, postischemic hyperemia was associated with an increase in CBF of 128%, 123%, and 129% of control in the rostral, middle, and caudal sections of the brain, respectively. In all treated groups and in the group receiving a tungsten-supplemented diet, BBB integrity was protected during reperfusion without inhibition of postischemic hyperemia. This study suggests that early disruption of the BBB to large molecules is mediated by free oxygen radicals, which inhibit rather than cause postischemic hyperemia.
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PMID:Effects of antioxidants on the blood-brain barrier and postischemic hyperemia. 775 39

To study the involvement of free oxygen radicals of the blood-brain barrier (BBB) disruption during early reperfusion, we isolated the distal internal carotid artery, and the middle and anterior cerebral arteries via the transorbital approach in anesthetized rabbits. Using radiolabeled microspheres, regional cerebral blood flow (rCBF) was measured before, during and after 1-hour unilateral occlusion of these vessels. Fifty-five minutes after ischemia, animals received intravenous saline placebo (control), superoxide dismutase (SOD) at 8 mg/kg = 30,000 U/kg, or weakened superoxide dismutase (wSOD) at 8 mg/kg = 30,000 U/kg. Integrity of the BBB was assessed by leakage of Evan's Blue-albumin dye (EB-albumin dye), which was given at 15 minutes of reperfusion and allowed to circulate for an additional hour. In the control and wSOD-treated groups, rCBF decreased (26% and 40% of control, respectively) within the blue-tinted tissue of the occluded hemisphere during ischemia; hyperemia was observed during early reperfusion. In the control and wSOD-treated groups, EB-albumin dye leakage across the BBB increased 49% within the occluded hemisphere. However, within the SOD-treated group, the BBB showed minimal dye leakage even though rCBF of the occluded hemisphere (so-called blue-tinted tissue) decreased by 38% during ischemia. We conclude that 1-hour focal cerebral ischemia and reperfusion produce a vascular endothelial injury at the BBB. Since SOD administration showed significant protection, free-oxygen-radical production during early reperfusion is associated with breakdown of the BBB to large molecules.
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PMID:Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain. 846 May 72

The "therapeutic window" of neuroprotective intervention due to hypoxic-ischemic brain injuries are initial disturbances of the neuronal function in regions of only moderate decrease of local cerebral blood flow (ICBF). Because of limited effects of single therapeutic principles therapeutic combinations should be tested. Neuroprotective effects of mild hypothermia and the nootropic drug Cerebrolysin (Cerebrolysin, EBEWE, Austria) on ICBF and development of brain edema were used. Four groups of adult Wistar rats (untreated and Cerebrolysin treated animals with 35 degrees C and 37 degrees C rectal temperature) were subjected to moderate forebrain ischemia by permanent bilateral carotid artery ligation for 6 h. The ICBF was measured continuously in the frontal and the occipital cortex by a 2-channel Laser Doppler flowmeter. The ECoG was derived from 4 ECoG leads above the frontal and occipital cortex and quantified by spectral analysis. Six hours after the onset of ischemia, the function of the blood-brain barrier to proteins was determined by staining with Evans Blue, the animals were sacrificed and the brain water content was estimated by gravimetry. Permanent bilateral carotid artery ligation led to an abrupt ICBF reduction to between 40-50% of baseline levels. Within a few minutes, however, the ICBF increased again to 50-80% of the baseline. The reduced spectral band power of the ECoG was correlated with the decreased ICBF values (p < 0.05) that indirectly indicated changes in the energy state of the neurons (p < 0.05). Changes in the ECoG appeared only with a delay of approximately 4 sec after the onset of ICBF reduction. Six hours after the onset of ischemia, a cytotoxic brain edema was shown in the frontoparietal cortex and hippocampus. Reducing the temperature by 2 degrees C diminished the decrease in ICBF between 10 min and 2 h after the onset of ischemia (p < 0.05). This effect was noted in the frontal but not in the occipital cortex. Furthermore, mild hypothermia prevented the loss of ECoG spectral power in the beta, alpha and theta bands (p < 0.05) as well as the development of cytotoxic brain edema. Cerebrolysin prevented the development of brain edema, too, both under normo- and hypothermic conditions. The ICBF was restored to higher levels in the occipital cortex in comparison both to the normothermic Cerebrolysin treated and hypothermic untreated rats (p < 0.05). This effect of Cerebrolysin was associated with only slight changes in ECoG, indicating that the neuronal activity state and the energy supply was obviously not decisively influenced. In conclusion, moderate ICBF reduction in rats to about 50-80% of baseline values was detectable in the ECoG by using spectral analysis. This reduction led to the development of cytotoxic brain edema in rats within 6 h. Thus, hypothermia prevents the development of cytotoxic brain edema. Cerebrolysin enhanced the effects of hypothermia on ICBF reduction and on the development of brain edema.
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PMID:Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats. 908 84

Brain swelling is a serious complication associated with focal ischemia in stroke and severe head injury. Experimentally, reperfusion following focal cerebral ischemia exacerbates the level of brain swelling. In this study, the permeability of the blood-brain barrier has been investigated as a possible cause of reperfusion-related acute brain swelling. Blood-brain barrier disruption was investigated using Evans Blue dye and [14C]aminoisobutyric acid autoradiography in a rodent model of reversible middle cerebral artery (MCA) occlusion. Acute brain swelling and cerebral blood flow (CBF) during ischemia and reperfusion were analyzed from double-label CBF autoradiograms after application of the potent vasoconstrictor peptide endothelin-1 to the MCA. Ischemia was apparent within ipsilateral MCA territory, 5 min after endothelin-1 application to the exposed artery. Reperfusion, examined at 30 min and 1, 2, and 4 h, was gradual but incomplete within this time frame in the core of middle cerebral artery territory and associated with significant brain swelling. Ipsilateral hemispheric swelling increased over time to a maximum (>5%) at 1-2 h after endothelin-1 but was not associated with a significant increase in the ipsilateral transfer constant for [14C]aminoisobutyric acid over this time frame. These results indicate that endothelin-1 induced focal cerebral ischemia is associated with an acute but reversible hemispheric swelling during the early phase of reperfusion which is not associated with a disruption of the blood-brain barrier.
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PMID:Influence of ischemia and reperfusion on the course of brain tissue swelling and blood-brain barrier permeability in a rodent model of transient focal cerebral ischemia. 934 60

Nitric Oxide's (NO) function in vasomotor control, inflammation, and signal transduction makes it an attractive potential mediator of the capillary leak seen in acute lung injury. Despite extensive study, the role of NO in intestinal ischemia/reperfusion-induced capillary leak remains controversial. Rats were treated with vehicle, norepinephrine, or L-NNA (nitric oxide synthase inhibitor) and then underwent sham laparotomy or 30 min SMA occlusion followed by 1 to 12 h of reperfusion. Evan's Blue dye was administered 1 h before animals were euthanized. Ratios of bronchoalveolar lavage or small-intestine lavage to serum dye concentrations were calculated as measures of capillary leak. Circulating neutrophil activation was measured with a nitroblue tetrazolium reduction assay. In vehicle-treated animals, both capillary leakage and PMN activation peaked at 4 h of reperfusion. These parameters returned to baseline by 12 h. Treatment with L-NNA accelerated ischemia/reperfusion-induced PMN activation as well as accelerated capillary leak from 4 to 1 h. Treatment with norepinephrine (hypertensive control) increased the magnitude of lung capillary leak but had no effect on the timing of ischemia/reperfusion-induced PMN activation or ischemia/reperfusion-induced capillary leak. These data show that intestinal ischemia/reperfusion-induced systemic capillary leak is associated with systemic neutrophil activation. Nitric oxide synthase inhibition accelerates ischemia/reperfusion-induced capillary leak and mediates the capillary leak seen in acute lung injury by modulating neutrophil activation.
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PMID:Nitric oxide mediates acute lung injury by modulation of inflammation. 973 31

Tumor necrosis factor (TNF) is released during hepatic ischemia/reperfusion (I/R) and plays an important role in the ensuing neutrophil-mediated lung and liver injury. Since TNF is not a direct neutrophil chemotaxin, we hypothesized that TNF may up-regulate neutrophil adhesion molecules, specifically intercellular adhesion molecule-1 (ICAM-1), following hepatic I/R, and that this molecule then plays an important role in tissue neutrophil influx. Rats underwent 90 min of lobar hepatic ischemia with reperfusion. Pulmonary and hepatic ICAM-1 expression were assessed by reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemical staining. Increases in hepatic ICAM-1 were demonstrated within 1 h of reperfusion, while increases in pulmonary ICAM-1 were not seen until 6 h of reperfusion. Next, rats were treated with anti-TNF antibody or control antibody without TNF neutralizing properties prior to hepatic I/R. Pretreatment with anti-TNF antibody significantly decreased pulmonary and hepatic ICAM-1 expression after hepatic I/R. We next investigated the effects of pretreatment with anti-ICAM-1 antibodies on the lung and liver injury that follows hepatic I/R. Lung injury was assessed by changes in pulmonary capillary permeability as estimated by extravasation of Evans Blue dye and pulmonary neutrophil influx as measured by lung myeloperoxidase levels. Liver injury was assessed by hepatic neutrophil morphometrics and plasma liver enzymes (alanine aminotransferase). Pretreatment with anti-ICAM-1 antibodies significantly decreased pulmonary capillary permeability, pulmonary myeloperoxidase, hepatic neutrophil influx, and plasma alanine aminotransferase, as compared to animals pretreated with control antibody. These data suggest that TNF is a proximal trigger for pulmonary and hepatic ICAM-1 up-regulation following hepatic ischemia with reperfusion, and that ICAM-1 is important for pulmonary and hepatic neutrophil influx, with the resultant tissue injury, following hepatic I/R.
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PMID:Tumor necrosis factor up-regulates intercellular adhesion molecule 1, which is important in the neutrophil-dependent lung and liver injury associated with hepatic ischemia and reperfusion in the rat. 974 46


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