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Query: UMLS:C0917798 (cerebral ischemia)
17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Global cerebral ischemia is well known to cause neuronal necrosis in selectively vulnerable sectors of the hippocampus. Since the hippocampus of the rat is involved in spatial navigation, learning, and memory, selective deficits in these abilities may arise from ischemic brain damage. Previous studies have shown (a) a detectable neurobehavioural deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus and (b) a reduction of ischemic neuronal necrosis with the noncompetitive N-methyl-D-Aspartate (NMDA) antagonist MK-801. This study was designed to determine the relationship between the improvement in structural brain damage in postischemically treated rats and any improvement in neurobehavioural performance, using a learning-set water task. Seventeen male Wistar rats received 10.5 min of forebrain ischemia induced by carotid clamping and hypotension. Brain temperature was estimated with probes in the temporalis muscle. Ten of these animals received no therapy (controls), and seven animals received 5 mg/kg MK-801 iv, 20 min postischemia. Six additional rats underwent a sham operation. Postischemic hypothermia was prevented with heating lamps. Four controls and one MK-801 treated animal died. The survivors were then tested on a place learning-set task in a swimming pool paradigm, and quantitative histopathologic analysis of their entire brains was done. The learning-set task revealed defects in spatial navigation, reflected as increased errors and latency in the performance of the untreated control rats. The performance of the MK-801 treated group progressively approached that of sham-operated rats over the course of testing and was significantly better than controls. Importantly, no long-term detrimental effect of MK-801 on the learning-set task performance was seen. Quantitative neuropathology revealed significantly less damage in the MK-801 treated group in all major brain regions. In the hippocampus, MK-801 treated animals showed hippocampal damage limited to the vulnerable portion of the pyramidal cell band comprising 48.8% of the CA1 pyramidal cells, as opposed to 72.4% in untreated controls. Extra-hippocampal damage was evident only in untreated control animals. MK-801 totally prevented neuronal necrosis in both the cerebral cortex and striatum and also prevented infarction in the neocortex and thalamus. Three conclusions emerge from the study. First, postischemic MK-801 mitigates structural brain damage in several brain regions in the absence of concomitant hypothermia. Second, neurobehavioural performance appears to be improved by MK-801 when performance trends are examined, but is somewhat less sensitive than quantitated histopathology due to compounding interanimal variation in performance abilities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The relationship of structural ischemic brain damage to neurobehavioural deficit: the effect of postischemic MK-801. 220 May 95

GIK (glucose-insulin-potassium) solution has been administered to myocardial infarction patients as a polarizing therapy, but the effects of GIK administration on vasospasm after subarachnoid hemorrhage have never been reported. We used GIK solution to treat 7 cases of symptomatic vasospasm with congestive heart failure due to hypervolemia-hypertensive treatment. The GIK solution, composed of 200cc of 50% glucose solution, 250cc of water, 40 mEq of KCl, and 20 units of actrapid insulin, was administered continuously through a central venous catheter. The GIK therapy improved congestive heart failure following elevation of cardiac output in 7 cases, and simultaneously stabilized the serum glucose level within the range of 88-175 mg/dl. After GIK administration, remarkable improvement in the consciousness level was achieved in all cases, and cerebral infarction due to vasospasm appeared in only one case in spite of severe subarachnoid hemorrhage. It is thought that GIK therapy will be effective in the treatment of symptomatic vasospasm with congestive heart failure through the normalization of hemodynamics, the improvement of hyperglycemia and protection against cerebral ischemia.
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PMID:[Treatment of symptomatic vasospasm with GIK (glucose-insulin-potassium) infusion]. 220 88

We studied how changes in BBB function are related to the development of ischemic brain edema. Focal cerebral ischemia was produced by left MCA occlusion in rats. The permeability of the BB to small or large molecules was evaluated qualitatively by the extravasation of EB or NaFl dyes and quantitatively by the uptake index of 125I-BSA or 14C-sucrose. Brain water content was determined by specific gravity. Measurements were made from the cortical core of the MCA territory within 14 days of occlusion. Water content progressively increased within 2 days of occlusion and then gradually decreased up to 14 days. Lightly stained EB areas were located only in the proximal portion of the ischemic core. The incidence of NaFl extravasation was similar to that of EB within 2 days of occlusion but was greater than that of EB 3 days after occlusion. NaFl staining diffusely extended into the ischemic core. Although the index of 125I-BSA increased only slightly within 2 days of occlusion, a marked increase in 125I-BSA was found after 3 days. The index of 14C-sucrose increased gradually after occlusion, reaching a peak at 8 days. These findings indicate that the change in BBB permeability is minimal in ischemic brain tissue when the accumulation of edema fluid is maximal and suggest that BBB alteration in ischemic brain tissue may be associated with the stabilization or resolution of the ischemic lesion.
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PMID:Role of blood-brain barrier permeability in focal ischemic brain edema. 239 29

We studied how the osmotic pressure gradient between blood and the brain is related to the development of ischemic brain edema. Focal cerebral ischemia was produced by left MCA occlusion in rats. Brain osmolality was determined with a vapor pressure osmometer, water content of the brain tissue was measured by wet and dry weight, and the tissue sodium and potassium contents were assayed by flame photometry. Permeability of BBB was tested by EB. These measurements were made from the cortical core of MCA territory at various intervals from 1 hr to 14 days after occlusion. Brain osmolality increased from 311 +/- 2 mOsm/kg (M +/- SE) to 329 +/- 2 mOsm/kg (n = 7, p less than 0.01) by 6 hrs after occlusion. Serum osmolality did not significantly change. The osmotic gradient between blood and the brain was about 26 mOsm/kg. Brain osmolality then decreased to 310 +/- 2 mOsm/kg by 12 hr after occlusion and remained about the same level for up to 14 days. Water content progressively increased within 1 day, then gradually decreased by 14 days. Sodium plus potassium content of the brain tissue did not increase and EB extravasation was not seen within 6 hr of occlusion. These findings indicate that an osmotic pressure gradient contributes to the formation of edema only during the early stage of cerebral ischemia. Brain osmolality is not related to tissue electrolyte change and BBB disruption to protein.
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PMID:An osmotic gradient in ischemic brain edema. 239 67

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema]. 246 14

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.
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PMID:Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats. 247 24

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.
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PMID:Effect of MCI-186 on brain edema in rats. 250 9

The effects of 3-methyl-1-(5'-oxohexyl)-7-propylxanthine (propentofylline, HWA 285) on transient cerebral ischemia were studied in Mongolian gerbils by measuring the in vivo 31P nuclear magnetic resonance (NMR) spectra and cerebral water content. Transient ischemia was produced by bilateral common carotid artery occlusion for 30 min, which was followed by 60 min of reperfusion. Propentofylline (1, 2.5 or 30 mg/kg) or normal saline was administered intravenously at 2 min after the reperfusion. The 31P spectra during the occlusion showed a marked reduction in adenosine triphosphate (ATP) and phosphocreatine (PCr) with elevation of inorganic phosphate (Pi) in all groups. The intracellular pH (pHi) calculated from the chemical shift of Pi was markedly reduced in all groups. After the reperfusion, ATP, PCr, Pi and pHi gradually recovered towards the normal levels in the control group. In the 2.5 mg/kg propentofylline group, the energy recovery was significantly faster than in the controls. The cerebral water content measured at the end of reperfusion was significantly lower in the 2.5 mg/kg propentofylline group than in the controls. However, such cerebral protective effects were not observed in the 1 mg/kg and 30 mg/kg groups. The present results suggest that propentofylline may accelerate the energy recovery of the transiently ischemic brain and suppress the development of post-ischemic cerebral edema. The effects, however, were not dose-dependent in manner. The detailed mechanism of the effects requires further investigation.
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PMID:Effects of propentofylline on energy metabolism of the ischemic brain studied by in vivo 31P nuclear magnetic resonance spectroscopy. 251 Jul 44

Stroke is a major cause of morbidity and mortality in the United States with 250,000 cases per year. Cerebral ischemia is the largest category of stroke with cardiac arrest, profound hypotension, and vascular occlusion the principal causes. Traditional approaches to the treatment of ischemic stroke focus on maintaining cardiac output, blood pressure, cerebral blood flow, and on preventing thrombosis. Recently, attention has been focused on developing new therapies that are directed toward abnormal biochemical events at excitatory synapses. Ischemia causes impairment of brain energy metabolism and the release of excessive amounts of glutamate into the extracellular space. This process secondarily excites neurons and further depletes energy stores. The excitotoxic hypothesis of brain injury proposes that glutamate is a principal cause of damage in ischemia. Three components of this hypothesis have been tested and largely proved in experimental studies in tissue culture and in animal models of stroke. First, elevated concentrations of glutamate cause excessive excitation at a subset of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor. Second, excitation at this receptor leads to excessive influx of sodium chloride and water which causes acute neuronal damage, and calcium which causes delayed and more permanent damage. Third, pharmacologic blockade at the NMDA receptor-ion channel complex prevents ischemic neuronal damage. Studies using specific pharmacologic compounds that block glutamate's action hold particular promise for treating stroke in humans, including competitive antagonists at the NMDA glutamate binding site (for example, 2-amino-5-phosphonovalerate, AP5), noncompetitive antagonists at the calcium channel (for example, MK-801, dextromethorphan, ketamine), and agents that might be directed at the glycine, zinc, and magnesium sites.
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PMID:Selective vulnerability of the brain: new insights into the pathophysiology of stroke. 254 55

Human plasma leukotriene C4 (LTC4) levels of cerebral infarcted patients showed a significant increase and plasma vitamin A (VA) levels showed a significant decrease compared to the normal plasma obtained from age-matched control. Therefore, the effect of VA on leukotriene (LT) levels and the progress of cerebral edema were investigated in VA deficient Wistar rat brains. Incomplete global cerebral ischemia was induced by occluding the bilateral common carotid arteries (BLCO) with clips. Wistar rats were made VA deficient by feeding them a vitamin A deficient diet for 5 weeks on a specific pathogen free status. After 3 hours of BLCO the blood was reperfused by removing the clips. After each period of reperfusion, the rat brain was fixed by freezing in situ and used for assaying leukotrienes, vitamin A, and water content. Slow reacting substance of anaphylaxis (LTC4 + LTD4 + LTE4) levels showed an increase at the end of BLCO in the VA deficient group and the high levels persisted for 30 min and then decreased to the control level. Brain water contents were elevated significantly at the 30 min phase of reperfusion. With VA administration, the water contents tended to be lower than in the VA deficient group at any phase. Histologically, after ischemia and reperfusion, evans blue extravasation and marked spongioid formations around small vessels were observed in the VA deficient rats only. These facts indicate that VA functions to stabilize cell membranes and suppress ischemic cerebral damage.
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PMID:[The effect of vitamin A on leukotriene production in the ischemic rat brain]. 260 50

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