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

Zinc is a potent inducer of the 72 kD heat shock protein (HSP72). In brain, pathological conditions such as ischemia and seizures increase extracellular zinc. The present study examines the effect of zinc on HSP72 expression in rat primary cortical astrocyte culture. Astrocytes were grown to confluence and exposed to zinc chloride in CO2-equilibrated Earle's buffered salt solution. Expression of HSP72 was examined using immunocytochemistry. HSP72 was induced with zinc concentrations of 5 to 100 microM after 4 h exposures, or 200 to 300 microM after 15 min exposures. At the lower concentrations expression occurred in small clusters of contiguous cells. At concentrations high enough to cause cell death, HSP72-positive astrocytes formed a continuous margin around patches of dead cells. These patterns of HSP72 expression are similar to the patterns seen after cerebral ischemia in vivo. Exposure to zinc at 100 microM for 4 h or 400 microM for 15 min caused greater than 90% cell death. Increases in extracellular zinc may contribute to HSP72 induction and astrocyte death under ischemia and other pathological conditions in brain.
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PMID:Zinc toxicity and induction of the 72 kD heat shock protein in primary astrocyte culture. 133 69

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.
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PMID:Ischemia-reperfusion does not affect reactivity of isolated canine basilar artery. 187 14

Hyponatremia frequently complicates the care of neurosurgical patients and requires prompt effective therapy. These patients commonly fulfill the laboratory criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting; the classification depends on the volume status of the patient. The authors have been dissatisfied with the standard therapy of fluid restriction for the critically ill neurosurgical patient because of 1) slow rates of sodium correction; 2) poor applicability in patients requiring multiple intravenous medications and/or nutritional support; and 3) possible dangers of inducing or enhancing cerebral ischemia in patients who already may be fluid-depleted. Reported successes in the treatment of hyponatremia due to SIADH by administration of urea and normal saline led to the authors' routine use of this therapy for hyponatremic neurosurgical patients. A retrospective review of an 18-month period revealed 48 patients (3% of all neurosurgical inpatients) with hyponatremia from various causes who received 62 treatments of urea and normal saline. Treatment consisted of 40 gm urea dissolved in 100 to 150 ml normal saline as an intravenous drip every 8 hours and an intravenous infusion of normal saline at 60 to 100 ml/hr for 1 to 2 days. The mean pretreatment serum sodium level (+/- standard deviation) was 130 +/- 3 mmol/liter (range from 119 to 134 mmol/liter). There was a significant mean posttreatment elevation to 138 +/- 4 mmol/liter (range 129 to 148 mmol/liter) (p less than 0.001, Student's t-test). Average daily fluid intake and output on treatment days were 2719 +/- 912 and 2892 +/- 1357 ml, respectively. There were no treatment complications in this group. It is concluded that urea and saline administration results in a rapid, safe, and effective correction of hyponatremia, making this method superior to fluid restriction in many neurosurgical patients.
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PMID:Administration of intravenous urea and normal saline for the treatment of hyponatremia in neurosurgical patients. 280 38

In a pilot study, 26 patients with acute completed strokes (48 hours to 5 days after cerebral infarction) were randomly assigned to the prostacyclin (PGI2) or placebo groups. PGI2 sodium salt (Epoprostenol, Wellcome Research Laboratories and Upjohn Company) or its solvent (glycine buffer) were infused into the subclavian vein for six-hour periods in five courses separated by six-hour intervals. Prostacyclin was administered at a rate of 2.5-5.0 ng/kg/min. A significant alleviation of neurological deficits occurred 6 and 54 hours after the treatment in patients receiving prostacyclin. This improvement lost its statistical significance at the end of a two-week observation period. It is concluded that further modified controlled studies are required to evaluate the therapeutic usefulness of PGI2 in the treatment of patients with cerebral ischaemia.
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PMID:Double-blind controlled trial of the therapeutic effects of prostacyclin in patients with completed ischaemic stroke. 390 21

Sixty-three mongrel dogs were exposed to 8-10 min. of complete cerebral ischemia with Aortic occlusion balloon catheter and followed by 120 min. of recirculation. The degree and distribution of post-ischemic reperfusion in 11 different cerebral regions were then assessed using radioactive labelled microspheres (15 +/- 3 micrometers). The animals were divided into 3 groups by the administration of drugs as follows: 1) no additional drugs; 2) Indomethacin (selective inhibitor of cyclooxygenase) 4 mg/kg 5 min. after ischemia; 3) Pyridine deriv. (OKY-1580 Na-salt, selective inhibitor of thromboxane synthetase) infusion 100 gamma/kg/min. beginning 5 min. after ischemia. Animals receiving no additional drugs had low cerebral blood flow rates at 120 min. after ischemia especially in basal ganglia and cerebral cortex. Animals receiving Indomethacin did not differ significantly from the no additional drug group. The significant enhancement and redistribution of post-ischemic reperfusion at 120 min. after ischemia occurred in animals receiving Pyridine deriv. with reversal of the state of poor reperfusion. These observations implicate an imbalance of prostaglandin pathways in platelets and blood vessel walls in the genesis of impaired post-ischemic reflow and suggest the usefulness of Pyridine deriv. in the treatment of local vasoconstriction of the brain after total cerebral ischemia.
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PMID:[Cerebral blood flow after total cerebral ischemia in dog (author's transl)]. 733 24

The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists, respectively, were compared both singularly and in combination in models of transient severe forebrain and transient focal cerebral ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30 minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7 days. This effect was not obtained with the intraperitoneal administration of either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at the same time intervals. This effect of intraperitoneal NBQX alone was reproduced in a two-vessel occlusion/hypotension model using this same drug administration. Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the combination of NBQX and MK-801 given after a delay, produced a significant reduction in the mean volume of neocortical infarction after transient focal ischemia. We conclude that the AMPA receptor may play a more important role than the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and in neocortical infarction. AMPA antagonists should be subjected to clinical stroke trials.
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PMID:AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA antagonists? 750 38

BW619C89 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5- trichlorophenyl)pyrimidine is a use-dependent blocker of voltage-dependent sodium channels that blocks veratrine-induced glutamate release in vitro. The aim of this study is to determine if BW619C89 inhibits glutamate release and is neuroprotective in cerebral ischemia produced by proximal middle cerebral artery (MCA) occlusion in rats. Infarct volume was determined at 24 hr after permanent MCA occlusion from 2,3,5-triphenyltetrazolim hydrochloride-stained sections. Pretreatment with BW619C89 (10, 20, 30 and 50 mg/kg i.v. of mesylate salt) decreased infarct volume in a dose-dependent fashion maximal at 30 mg/kg compared to saline controls. Treatment with 30 mg/kg up to 45 min after MCA occlusion also was effective. Microdialysate glutamate in rats treated with 30 mg/kg of drug before MCA occlusion was decreased in both caudate (ischemic core) and rostral cortex (penumbra) compared to controls. BW619C89 did not induce significant arterial hypotension, except when it was administered by rapid bolus administration. In this case, the hypotension was transient and did not reduce efficacy or superficial cortical blood flow. BW619C89 did not induce the 72 kD heat shock protein in cingulate gyrus or retrosplenial cortex as did MK801, suggesting that BW619C89 does not injure neurons in these regions as do N-methyl-D-aspartate antagonists. These results suggest that inhibition of glutamate release by BW619C89 may be an effective and nontoxic treatment for stroke.
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PMID:Neuroprotective effects of a use-dependent blocker of voltage-dependent sodium channels, BW619C89, in rat middle cerebral artery occlusion. 791 Feb 13

Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC-K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke.
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PMID:Effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1- benzopyran-6yl-hydrogen phosphate] potassium salt on cerebral energy state and consciousness recovery following transient forebrain ischemia in gerbils. 798 54

To evaluate the role played by nitric oxide in global cerebral ischaemia we examined the effects of 7-nitroindazole and a sodium salt of 7-nitroindazole (inhibitors of neuronal nitric oxide (NO) synthase) and NG-nitro-L-arginine methyl ester (a more general inhibitor of NO synthase) in the gerbil model of cerebral ischaemia. Four experiments were carried out. In the first experiment, animals were either sham-operated, subjected to 5 min bilateral carotid occlusion (BCAO) or administered 7-nitroindazole or NG-nitro-L-arginine methyl ester immediately after occlusion followed by three further doses at 3, 6 and 24 h post-occlusion. In the second experiment, we examined the effects of a sodium salt of 7-nitroindazole, which is more soluble than 7-nitroindazole, using the same protocol. In the third experiment, the effects of the sodium salt of 7-nitroindazole administered at 10 mg/kg at 0, 3, 6, 24, 27, 30, 33, 52, 55, 72, 75 and 78 h post-occlusion or at 0.05 mg/h for 72 h via mini-pumps were evaluated. In separate experiments, we examined the effects of three reference compounds dizocilpine (MK-801), 2, 3-dihydroxy-6-nitro-7-sulphamoyl-benz(F)-quinoxaline (NBQX) and eliprodil using the same model. Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5 min bilateral carotid occluded animals 5 days after surgery. Both 7-nitroindazole and NG-nitro-L-arginine methyl ester provided significant neuroprotection (P < 0.01) against this neuronal death. The sodium salt of 7-nitroindazole showed no protection when administered up to 12 times post-occlusion, but did provide significant (P < 0.01) neuroprotection when administered via mini-pump. The neuroprotection was similar to that provided by MK-801 and eliprodil, but not as good as that observed with NBQX. These results indicate that nitric oxide plays a role in ischaemic cell death and that selective neuronal nitric oxide synthase inhibitors can protect against ischaemic brain damage.
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PMID:Neuroprotective effects of 7-nitroindazole in the gerbil model of global cerebral ischaemia. 888 6

Hyponatremia, natriuresis, and a decrease in plasma volume of greater than 10% occurs in approximately 50% of the patients with aneurysmal SAH, perhaps due to SIADH and CSWS. However, fluid restriction, as indicated in SIADH, might result in vasospasm and cerebral infarction in these patients. Maintaining intravascular volume seems to be important in SAH; several reports suggest that cerebral ischemia can be reversed by use of volume expanders. Fludrocortisone has been shown to reduce natriuresis, which may help maintain plasma volume in patients with SAH. Adequate oral salt intake also appears to have possible therapeutic benefit in these patients. However, it remains unproven whether fludrocortisone results in a decreased incidence of cerebral ischemia. Larger controlled trials are needed to ascertain the impact of fludrocortisone on prevention of cerebral ischemia in patients with SAH.
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PMID:Fludrocortisone in the treatment of subarachnoid hemorrhage-induced hyponatremia. 916 63


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