Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lubeluzole is a neuroprotective compound in the final stages of clinical evaluation. We evaluated the effects of intravenous followed by intraperitoneal doses of lubeluzole on histological outcome after reversible tandem middle cerebral/common carotid artery occlusion in Long-Evans rats, with particular emphasis on the time window of efficacy. Lubeluzole, started 15 min after the onset of ischemia, had no adverse physiological or behavioral effects and reduce maximal infarct volume produced by 120 min or more of arterial occlusion by approximately 50%, from 143.2 +/- 11.8 mm3 (p < 0.05). Lubeluzole did not prolong the duration of middle cerebral artery occlusion which could be tolerated before histological damage occurred. Lubeluzole was still effective if started 30 min after the onset of ischemia (34% reduction of maximal infarct volume; p < 0.05), but not after delays of 60 or 120 min. we conclude that lubeluzole has promise as a neuroprotective drug, particularly for more severe strokes, but must be started very rapidly after the onset of ischemia to be effective.
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PMID:Treatment of experimental focal ischemia in rats with lubeluzole. 888 77

In order to determine the effect of depleting circulating polymorphonuclear neutrophils (PMN's) on brain microcirculation and lesion size in an acute stroke model, Spontaneously Hypertensive Rats (SHR) were injected intraperitoneally with either 2 ml RP-3 antineutrophil antibody followed in 4 hours by MCAO (n = 5), 2 ml saline followed in 4 hours by middle cerebral artery occlusion (MCAO) (n = 6), or 2 ml saline followed in 4 hours by sham operation (n = 3). After 4 hours of ischemia or a 4 hour interval (sham-operated animals), microvascular perfusion was assessed by means of an intravascular fluorescent tracer technique: FITC-dextran and Evans blue were injected intravenously 10 seconds and 5 seconds, respectively, before decapitation. Lesion volume was calculated by interpolation from histologic sections cut from 8 predefined stereotactic levels. MCAO with the normal complement of neutrophils led to significant impairment of perfusion in nutrient vessels and a maximal ischemic lesion volume. Depletion of circulating leukocytes by RP-3 significantly attenuated the microvessel perfusion impairment and reduced the volume of ischemic brain injury.
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PMID:Polymorphonuclear leukocytes and microcirculatory perfusion in acute stroke in the SHR. 889 68

Oxidative stress, assessed by tissue ascorbate loss following ischemia, is greater in male than female rat brain. The factors mediating this gender difference are unclear. The goal of the present studies was to determine the influence of gonadal sex hormones on this difference. Three weeks prior to experiment, adult Long-Evans male and female rats were gonadectomized for comparison with controls. Ascorbate and glutathione levels were determined in brain and plasma under basal conditions and in brain after one-hour decapitation ischemia, using liquid chromatography with electrochemical detection. Basal ascorbate levels in brain were 6-9% higher in males than in females, whereas plasma levels were 100% higher in males. After gonadectomy, the gender difference in plasma ascorbate levels was lost, while the effect on basal brain levels depended upon region. Ischemia-induced losses in brain ascorbate were three-fold greater in control males compared to control females. Significant losses occurred in frontal cortex, hippocampus, and cerebellum in males during ischemia, whereas loss in females was significant in cerebellum only. After gonadectomy, increased ascorbate loss was seen in all female brain regions, indicating enhanced oxidative stress. This increase eliminated the gender difference in loss; male ascorbate loss was comparatively unaffected by gonadectomy. Glutathione levels and loss were unaffected by either gender or gonadectomy, indicating differences in regulation from that of ascorbate. These findings provide evidence for the hypothesis that protection against oxidative stress is afforded by ovarian sex hormones, thus decreasing the potential for oxidative cell damage in females compared to males.
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PMID:Enhanced oxidative stress in female rat brain after gonadectomy. 894 21

Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.
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PMID:Polyamines induce blood-brain barrier disruption and edema formation in the rat. 898 32

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
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PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7

Catalase activity was evaluated in Long Evans rat retina after ischemia and reperfusion. Ischemia was induced by ligation of the optic nerve and vessels. Rats were sacrificed after 15 and 120 min of reperfusion, respectively. Catalase activity was assessed by Claiborne's method and was expressed as U/mg of protein. In the first group, retinas of each animal were pooled. In the second group, ischemia was induced in the right eye with the left eye serving as control. In the first group, enzyme activity was 7.39 +/- 0.26 (n = 11), 7.67 +/- 0.27 (n = 9) and 9.15 +/- 0.45 (n = 7) for the sham-operated, 15- and 120-min reperfusion groups, respectively. There was a significant difference between the control and 120-min reperfusion groups (p < 0.001). In the second group, there was a significant (p < 0.01) increase in catalase activity in the ischemic eye compared to the non-ischemic eye after 15 (n = 7) and 120 min (n = 9) of reperfusion. These findings may suggest a rapid activation of catalase activity during the ischemia-reperfusion sequence.
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PMID:Changes of catalase activity after ischemia-reperfusion in rat retina. 903 90

To examine the changes in blood-brain barrier (BBB), cerebral microcirculation, and histology from 15 min to 72 h after decompression, 90 rats were exposed to experimental compression to 6 atm abs air for 90 min and subsequent rapid decompression. The disruption of BBB was examined by Evans blue extravasation. The cerebral microcirculation was demonstrated by perfusion with India ink. The area stained with Evans blue and the regions of defective filling with India ink, observed immediately after decompression decreased in size with time and were undetectable 3-24 h after decompression. The edematous brain tissue with enlarged perivascular space and darkly stained nerve cells also decreased to the uncompressed control level 1-24 h after decompression. These reversible dysbaric changes, however, reappeared 48-72 h after decompression. The different mechanisms, the physicochemical effects of microbubbles, and the maturation phenomenon after temporary brain ischemia induced by dysbaric microbubbles may be involved in the brain damage after decompression sickness.
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PMID:Reversibility in blood-brain barrier, microcirculation, and histology in rat brain after decompression. 906 51

The aim of this study was to describe the normal distribution of the water content in several regions of the rat brain and furthermore to determine if global ischemia results in a variable increase in water content in these regions. Water content was determined in 40 regions; in 8 unaffected brains by gravimetry and in 9 unaffected brains by estimation of the wet/dry weight ratio. In addition, 6 rats underwent 6 h of moderate global brain ischemia in order to evaluate the sensitivity of the investigated brain areas to develop a cytotoxic brain edema. The impermeability of the blood-brain barrier to proteins was evaluated by staining with Evans blue. Physiological differences in water content between the several brain regions ranged from 72.57 +/- 0.77% (mean +/- S.D.) in the medulla oblongata to 84.83 +/- 0.52% in the hypothalamus. Generally, the water content of the grey matter was higher than that of the white matter and increased from the frontal to the occipital and from the parietal to the basal cortex. Even adjacent cortical regions showed differences in the amount of brain water of up to 3.41%. In the ischemic animals, the impermeability of the blood-brain barrier to proteins was not compromised, but an increase in the amount of brain water was found in the frontoparietal cortex of 1.17 +/- 0.37% and hippocampus of 1.49 +/- 0.39% (P < 0.05). This ischemic increase in the brain water content was small in comparison to the normal variance in regional brain water content. Similar results were obtained by determining the wet/dry weight ratio and by gravimetry. Gravimetry led to more consistent results. In conclusion, the study shows great differences in normal water content between the several brain areas in comparison to an only slight increase of water content due to the development of cytotoxic brain edema. The determination of an early state of an increased brain water content requires an adequate and differentiated measurement of different brain areas. The gravimetry fulfills this demand.
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PMID:The distribution of normal brain water content in Wistar rats and its increase due to ischemia. 907 Jun 30

Male Long-Evans rats were subjected to 7 min of chest compression (CC) to produce cardiac arrest and global ischemia resulting in damage to the brain. Timidity and motor activity were evaluated using the elevated plus maze, one of the most widely accepted methods for measuring anxiety in rats. Post-ischemic rats spent much less time in the open arms (3% at day 5) than handled (54%) or sham-compressed (30%) rats. This was interpreted as increased anxiety. Thus, post-ischemic rats developed more anxiety than normal handled rats or sham-operated rats. Anxiety increased markedly on post-ischemic day 2, suggesting a delayed effect. Anxiety gradually decreased after day 5 but recovery was still incomplete up to 115 days post-ischemia. Motor activity decreased gradually during days 2-5 post-ischemia and then recovered to the normal range after day 15. These results are inconsistent with damage limited to the hippocampus and suggest that less obvious histological changes may be occurring elsewhere in the brain.
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PMID:Ischemia-induced anxiety following cardiac arrest in the rat. 907 72

Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm2 calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.
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PMID:Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat. 913 19


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