Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High affinity [3H]ouabain binding was examined in the hippocampal CA1 region and frontal cortex of rats subjected to 5 min complete cerebral ischemia in a clinical death model, and to subsequent resuscitation. A decrease of Bmax directly after ischemia and its further gradual decrease during 120 min of reperfusion were noted in the ischemia-vulnerable CA1 region, whereas no change of Bmax was observed in frontal cortex. The apparent Kd constant showed insignificant fluctuations in either of the two brain regions. Since ouabain binds with high affinity to the neuronal (alpha +)-form of Na+/K+-ATPase, the results indicate a rapid enzyme loss in CA1 neurons. The high affinity ouabain binding test proved to be a sensitive detector of premorphological changes in nerve cell membranes in ischemia.
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PMID:Rapid decrease of high affinity ouabain binding sites in hippocampal CA1 region following short-term global cerebral ischemia in rat. 254 99

Neuronal cell degeneration was studied in vitro in primary rat brain neuronal cultures grown in serum-free, chemically defined, CDM R12 medium, by measuring lactate dehydrogenase (LDH) released in the culture medium. A Ca2+-dependent neuronal cell degeneration was observed after prolonged and transient exposure 30 microM veratridine. The release of LDH occurred gradually and could be completely prevented by 2 mM ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, 0.1 microM tetrodotoxin, and 1 microM flunarizine. Flunarizine was without effect on neuronal cell loss induced by 1 mM glutamate, 1 mM kainic acid, and 5 mM KCN. The lack of effect on neurotoxicity induced by 1 mM glutamate differentiates flunarizine from N-methyl-D-aspartate antagonists such as MK-801. The latter protected at nanomolar concentrations against glutamate-induced neuronal cell death but had a maximal effect only at 0.1 mM on the veratridine-induced released LDH. It is suggested that, besides the excitatory amino acid receptor pathway, prolonged opening of the veratridine-sensitive Na+ channel can be neurotoxic. The latter can be prevented by flunarizine. The role of Na+ channel blockers as therapeutic agents in cerebral ischemia is discussed.
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PMID:Ca2+-mediated neuronal death in rat brain neuronal cultures by veratridine: protection by flunarizine. 255 10

Ergot alkaloids are commonly used as cerebroprotective drugs. Their efficacy has been demonstrated experimentally in animals submitted to acute cerebral anoxia or ischaemia, at dose levels hugely superior to dose levels usually administered in humans. In the present experiments, dihydroergocryptine (DHEC), a constituent of dihydroergotoxine (DHET), was administered at doses closely related to human doses, preventively (in experiments where animals survived only for a short while after ischaemic insult) or curatively, and its efficacy tested through refined neurological and biochemical evaluation of experimental cerebral ischaemia sequelae. DHEC was administered orally (30 micrograms or 150 micrograms/kg body weight (bwt) twice daily) for 3 days, following transient cerebral ischaemia induced by a 60-min carotid occlusion plus sodium nitroprusside (1.1 mg/rat s.c.) injection, or, in a second experiment, prophylactically (60 micrograms or 300 micrograms/kg bwt/day) for 4 days prior to multiple cerebral infarct induced by sodium arachidonate injection into the left internal carotid artery. The neurological sequelae were evaluated by the Irwin visual placing response or by a battery of behavioural tests. Na-K-ATPase enzyme activity in cerebral homogenates was measured; decreases in this enzyme activity are considered to reflect the neuronal membrane consequences of the neurocell energetic metabolism alterations caused by cerebral ischaemia. Low dose oral DHEC treatment prevented the behavioural abnormalities and memory impairment arising after transient cerebral ischaemia and there was a marked trend in improving the behavioural abnormalities observed in animals submitted to massive cerebral infarction, in spite of the model severity. DHEC prevented reduction in cerebral Na-K-ATPase activity after cerebral multiinfarction. These effects of DHEC were observed with doses and administration route close to the usual therapeutic regimen.
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PMID:The effects of dihydroergocryptine on the neurological and enzyme disorders induced by cerebral ischaemia in rats. 255 45

A severe case of poisoning with hypertonic sodium chloride used as an abortifacient agent in a 23-years-old woman is described. ultrasonic examination during the 28th week of gestation indicated the anencephalic fetus. The patient underwent puncture of the posterior vaginal wall and instillation of the 25% sodium chloride. The patient successfully recovered from anesthesia, but 15 min later she became cyanotic, febrile, and comatose. Blood chemical analysis indicated abnormally high levels of sodium and chloride. Cytological examination of urine specimen showed elevated erythrocyte count. Computed tomography indicated bilateral foci of cerebral ischemia. Treatment included intravenous infusions of glucose solution, vitamin C and potassium chloride, administration of diuretics, diazepam and calcium gluconate. The patient was discharged 24 days later.
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PMID:[Sodium chloride poisoning during abortion]. 262 38

Hypertensive crisis is an acute emergency requiring aggressive management. Its incidence has decreased in recent years but still is prevalent in the medical community. From review of past and present treatment regimens, the following recommendations can be considered. (1) In the treatment of malignant hypertension with associated CHF, sodium nitroprusside is still an excellent agent. It has a rapid onset of action and blood pressure can be easily titrated. Nitroglycerin is also another agent that can be used in this situation. (2) In the treatment of malignant hypertension with associated aortic dissection, trimethophan camsylate is the preferred agent. An alternative choice is the combination of nitroprusside and labetalol. (3) In the treatment of malignant hypertension with associated myocardial ischemia, an excellent choice is nitroglycerin. Labetalol also should be considered in this situation. (4) In the treatment of hypertension during pregnancy, hydralazine is still a good choice. Labetalol has also been shown to be efficacious. (5) In the treatment of malignant hypertension with associated cerebral ischemia, the following drugs should be considered: nitroprusside, nitroglycerin, and labetalol. The most important attribute of these agents is that they are nonsedating and rapid in onset. (6) In the treatment of postoperative hypertension the choices best suited are labetalol, enalapril, nitroprusside, and nitroglycerin. These agents are rapid in onset and all can be administered intravenously.
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PMID:Hypertensive crisis. 267 90

In this study with randomized controls, we administered fludrocortisone acetate to 46 of 91 patients with subarachnoid hemorrhage in an attempt to prevent excessive natriuresis and plasma volume depletion. Fludrocortisone significantly reduced the frequency of a negative sodium balance during the first 6 days (from 63% to 38%, p = 0.041). A negative sodium balance was significantly correlated with decreased plasma volume during both the first 6 days (p = 0.014) and during the entire 12-day study period (p = 0.004). Although fludrocortisone treatment tended to diminish the decrease in plasma volume, the difference was not significant (p = 0.188). More patients in the control group developed cerebral ischemia (31% vs. 22%) and, consequently, more control patients were treated with plasma volume expanders (24% vs. 15%), which may have masked the effects of fludrocortisone on plasma volume. Fludrocortisone therefore reduces natriuresis and remains of possible therapeutic benefit in the prevention of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
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PMID:Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage. 267 26

In shock, the presence of hyperlactatemia is prognostic of a failure to survive. An experimental model of stroke that combines bilateral carotid ligation and bleeding to a mean arterial pressure of 50 mm Hg induces hyperlactatemia like that associated with tissue hypoperfusion of hemorrhagic shock. In previous nonsurvival studies with this model, post-ischemic treatment of fed rats with 25 mg/kg of sodium dichloroacetate (DCA) was effective in lowering brain tissue lactate but did not significantly affect the ischemia-induced increase in serum lactate measured after 30 minutes of ischemia followed by 30 minutes of reperfusion. Investigators using other animal models treated hyperlactatemia associated with tissue hypoperfusion successfully with a DCA dose of more than 25 mg/kg. Our goal was to determine the effect of a higher dose of DCA on serum lactate in the model of cerebral ischemia with systemic hypotension that we had used in previous studies. The previously unstudied dose-response also was evaluated in our study. Rats that had been fed ad libitum were assigned randomly to either a real or sham (control) ischemic group. Immediately after 30 minutes of ischemia and subsequent reinfusion of blood or after 30 minutes of sham ischemia, rats received DCA (0, 25, 50, 100, 200, or 300 mg/kg). Comparisons were made of blood values measured at the end of equilibration before ischemia, after 30 minutes of ischemia, and after 30 minutes of reperfusion. All ischemic rats were hyperlactatemic. Serum lactate levels were not correlated to blood glucose elevation during ischemia. After treatment in both control and ischemic rats, the percentage decrease in serum lactate varied as a logarithmic function of the DCA dose administered. Glucose levels and pH were not affected by DCA treatment at any dose. Because acidemia decreases lactate uptake by the liver, values for acidotic rats were compared with those for nonacidotic rats. Whereas lactate in acidotic rats decreased significantly only when treated with DCA, nonacidotic rats evidenced this decrease regardless of whether they received DCA. We discuss the relationship of these findings to the peak levels of lactate achieved, the resolution of hyperlactatemia, and factors that affect the interpretation of data in therapeutic studies using DCA.
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PMID:Effects of various doses of sodium dichloroacetate on hyperlactatemia in fed ischemic rats. 268 99

The role of kinins as mediator substances is increasingly recognized in cerebral ischemia and trauma. It has previously been shown that cerebral exposure to bradykinin, which causes brain edema, is associated with arteriolar dilatation and selective opening of the blood-brain barrier (BBB) to small molecular weight indicators, such as Na+-fluorescein. Since the evidence suggests that these effects results from an activation of the arachidonic acid cascade, particularly from formation of E- and I-type prostaglandins, therapeutical inhibition of the cerebral effect of bradykinin has been attempted by pretreatment of experimental animals with dexamethasone. The BBB function and changes of the pial vessel diameters were studied by fluorescence microscopy in cats in alpha-chloralose anesthesia during superfusion of the exposed cerebral cortex. After a control phase bradykinin was added to a cerebral superfusate in concentrations of 4 x 10(-8) M to 4 x 10(-3) M. Two additional groups of animals received dexamethasone in a dose of 1, or 5 mg/kg body wt., respectively, 5 h prior to the cerebral superfusion with bradykinin. Na+-fluorescein (mol wt.: 376) was infused intravenously as a BBB indicator. The BBB marker remained strictly confined to the intravascular compartment under control conditions. Pretreatment with dexamethasone did not prevent opening of the BBB by bradykinin, either at the low, or high dose. However, the low dose of dexamethasone blunted the vasodilatory response to bradykinin, whereas the high dose (5 mg/kg) was found to enhance the dilatory properties of bradykinin at concentrations of 4 x 10(-3) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood-brain barrier permeability and vascular reactivity to bradykinin after pretreatment with dexamethasone. 275 Apr 77

Sodium derived from the blood is known to accumulate in brain tissue during the early stages of incomplete ischemia. Our present studies were undertaken to determine the relation between blood-brain barrier sodium transport and the development of ischemic brain edema. Incomplete cerebral ischemia was produced in gerbils by ligation of the left common carotid artery under ether anesthesia. Following recovery from the anesthetic, the gerbis were evaluated for the presence of neurologic symptoms and were divided into symptomatic (n = 77) and asymptomatic (n = 94) groups. Tissue water, sodium, and potassium contents, tissue plasma volume, and brain uptake of 22Na were measured in both groups 1.5, 3, 6, 12, and 24 hours after carotid ligation. There was a progressive accumulation of sodium and water in the ipsilateral cerebral cortex of the symptomatic group compared with either the corresponding contralateral cortex of the same gerbils or with the asymptomatic group. Net changes in brain sodium and potassium concentrations appeared to be the main determinants of fluid accumulation. Brain edema was not due to opening of the blood-brain barrier because the unidirectional transport of 22Na remained low and was even reduced by 35-55% in the ischemic cortex. Nevertheless, this sodium transport activity appeared to be rate-limiting in the development of brain edema during the first 3 hours of ischemia because the rate of sodium accumulation in the tissue was the same as the rate of 22Na transport from the blood to the brain. We conclude that blood-brain barrier sodium transport is an important factor in the formation of ischemic brain edema.
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PMID:Blood-brain barrier sodium transport limits development of brain edema during partial ischemia in gerbils. 277 85

Nicardipine, a calcium antagonist of the 1:4 dihydropyridine type, has been used to treat angina and hypertension and is currently being examined as an agent for treating ischemia of cerebral and myocardial tissue. Nicardipine shows high affinity for the dihydropyridine binding site (pKi = 9.7) and inhibits the L-type calcium ion channel as demonstrated by its ability to decrease the calcium ion-dependent action potential dose-dependently in ventricular papillary muscle (pIC50 = 7.15). Nicardipine shows greater potency in inhibiting the response of vascular smooth muscle (pIC50 = 8.20) than that of cardiac muscle (pIC50 = 7.15). The nicardipine selectivity for vascular smooth muscle is greater than that shown by other dihydropyridine calcium antagonists such as nifedipine and accounts for the efficacy of nicardipine in the treatment of angina and hypertension. Various mechanisms have been proposed to account for the beneficial action of nicardipine in treating animal models of cerebral ischemia and myocardial infarction. For example, it has been suggested that (1) nicardipine has a specific membrane-stabilizing effect on cell membranes, (2) the compound blocks certain sodium channels, (3) it may become concentrated in ischemic cells, or (4) it may stimulate calcium ion efflux from mitochondria, and these actions may account for the inhibition by nicardipine of veratrine-induced contraction of myocytes. In this study, some of these effects of nicardipine were examined. However, the suggestion that nicardipine concentrates in ischemic cells owing to the tertiary amine structure could not be conclusively demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular action of nicardipine. 280 73


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