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

The neurotoxicity of glutamate and hypoxia was investigated in vitro on hippocampal neurons, which were obtained from 18-day-old rat fetuses and were maintained for 3 days in culture. Chemically defined medium without glutamate was used and the plating density was low enough that the effect of exogenously added glutamate could be directly evaluated. In the normal culture condition 1 mM glutamate was necessary to cause significant neuronal loss in the following 24 h. In marked contrast, when glutamate was added after subcritical hypoxic stress, a dose of glutamate as low as 10 microM could exhibit neurotoxicity. Administration of MK-801, a selective noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, could in part reverse this increased susceptibility to low-dose glutamate after hypoxia, although MK-801 could not protect hippocampal neurons from high-dose glutamate. Therefore, both the NMDA receptor and other subclasses of the glutamate receptor may be involved in this neurotoxicity of glutamate. Different mechanisms of glutamate neurotoxicity with high and low doses are discussed. Our results showed that hippocampal neurons exposed to subcritical hypoxia become more vulnerable to glutamate than those without hypoxia. This increased susceptibility is of great interest to understanding the mechanism of slowly ongoing neuronal loss caused by ischemia or epilepsy.
J Cereb Blood Flow Metab 1990 Nov
PMID:Hippocampal neurons become more vulnerable to glutamate after subcritical hypoxia: an in vitro study. 221 81

The effects of the N-methyl-D-aspartate (NMDA) antagonist MK-801 on capillary beds and CBF following 1 h of transient incomplete focal cerebral ischemia were studied by examining 133Xe CBF, capillary diameter, and area of perfused vasculature. Capillary diameter increased from a control of 5.24 +/- 0.37 to 8.62 +/- 0.57 microns (p less than 0.001) and area of perfused vasculature from 20,943 +/- 1,151 to 30,442 +/- 1,691 microns2/x 10 magnification field (p less than 0.001) with MK-801 1.0 mg/kg administered 30 min prior to ischemia. After flow restoration in control animals, there was a relative hypoperfusion with eventual normalization of CBF over 60 min. Alternatively, in MK-801 1.0 mg/kg animals, there was rapid normalization of CBF upon flow restoration without the postischemic hypoperfusion observed in controls. On histological analysis, there was consistently less neuronal edema in MK-801-treated animals. These results support the hypothesis that hypoperfusion following incomplete focal cerebral ischemia may be due in part to NMDA-mediated cellular edema with subsequent extravascular capillary bed compression.
J Cereb Blood Flow Metab 1990 Nov
PMID:MK-801 attenuates capillary bed compression and hypoperfusion following incomplete focal cerebral ischemia. 221 82

The effect of nimodipine pretreatment on CBF and brain edema was studied in conscious rats subjected to 2.5 h of focal cortical ischemia. An infusion of nimodipine (2 micrograms/kg/min i.v.) or its vehicle, polyethylene glycol 400, was begun 2 h before the ischemic interval and was continued throughout the survival period. Under brief halothane anesthesia, the animals' right middle cerebral and common carotid arteries were permanently occluded, and 2.5 h later, they underwent a quantitative CBF study ([14C]iodoantipyrine autoradiography followed by Quantimet 970 image analysis). Nimodipine treatment improved blood flow to the middle cerebral artery territory without evidence of a "vascular steal" and reduced the volume of the ischemic core (cortex with CBF of less than 25 ml/100 g/min) and accompanying edema by approximately 50% when compared with controls (p = 0.006 and 0.0004, respectively). Mild hypotension induced by nimodipine did not aggravate the ischemic insult. The ischemic core volumes, however, were 50-75% smaller than the 24-h infarct volumes generated in a similar paradigm that demonstrated 20-30% infarct reduction with continuous nimodipine treatment. These results suggest that nimodipine pretreatment attenuates the severity of early focal cerebral ischemia, but that with persistent ischemia, cortex surrounding the ischemic core undergoes progressive infarction and the early benefit of nimodipine treatment is only partly preserved.
J Cereb Blood Flow Metab 1990 Nov
PMID:Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia. 221 83

In a randomized double-blind placebo-controlled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1990 Jan
PMID:Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography. 229 28

Nearly complete brain ischemia under normoglycemic conditions results in death of only selectively vulnerable neurons. With prior elevation of brain glucose, such injury is enhanced to include pancellular necrosis (i.e., infarction), perhaps because an associated, severe lactic acidosis preferentially injures astrocytes. However, no direct physiologic measurements exist to support this hypothesis. Therefore, we used microelectrodes to measure intracellular pH and passive electrical properties of cortical astrocytes as a first approach to characterizing the physiologic behavior of these cells during hyperglycemic and complete ischemia, conditions that produce infarction in reperfused brain. Anesthesized rats (n = 26) were made extremely hyperglycemic (blood glucose, 51.4 +/- 2.8 mM) so as to create potentially the most extreme acidic conditions possible; then ischemia was induced by cardiac arrest. Two loci more acidic than the interstitial space (6.17-6.20 pH) were found. The more acidic locus [4.30 +/- 0.19 (n = 5); range: 3.82-4.89] was occasionally seen at the onset of anoxic depolarization, 3-7 min after cardiac arrest. The less acidic locus [5.30 +/- 0.07 (n = 53); range 4.46-5.93)] was seen 5-46 min after cardiac arrest. A small negative change in DC potential [8 +/- 1 mV (n = 5); range -3 to -12 mV and 7 +/- 2 mV (n = 53); range +3 to -31 mV, respectively] was always seen upon impalement of acidic loci, suggesting cellular penetration. In a separate group of five animals, electrical characteristics of these cells were specifically measured (n = 17): membrane potential was -12 +/- 0.2 mV (range -3 to -24 mV), input resistance was 114 +/- 16 M omega (range 25-250 M omega), and time constant was 4.4 +/- 0.4 ms (range 3.0-7.9 ms). Injection of horseradish peroxidase into cells from either animal group uniformly stained degenerating astrocytes. These findings establish previously unrecognized properties of ischemic astrocytes that may be prerequisites for infarction from nearly complete ischemia: the capacity to develop profound cellular acidosis and a concomitant reduction in cell membrane ion permeability.
J Cereb Blood Flow Metab 1990 Jan
PMID:Astrocytic acidosis in hyperglycemic and complete ischemia. 229 27

We investigated the effect of the known antagonist of platelet-activating factor (PAF), ginkgolide B, on postischemic neuronal damage in the rat. Neuronal necroses were evaluated in the hippocampus 7 days after a 10-min forebrain ischemia. Preischemic application of ginkgolide B (50 mg/kg p.o.) significantly reduced neuronal damage. It is suggested that the antagonism of PAF is responsible for this beneficial effect of ginkgolide B.
J Cereb Blood Flow Metab 1990 Jan
PMID:PAF antagonist ginkgolide B reduces postischemic neuronal damage in rat brain hippocampus. 229 30

Following a period of complete global cerebral ischemia and reperfusion there ensues a low flow state referred to as the delayed postischemic hypoperfusion state. It is unknown whether this low flow state contributes to neuronal injury or whether the magnitude of hypoperfusion correlates with the duration of ischemia. The latter question was addressed in 20 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 3, 9, 12, or 18 min. Following reperfusion, CBF (by sagittal sinus outflow) and CMRO2 were determined for 90 min, and results were correlated with the duration of ischemia. At 90 min postischemia the magnitude of decrease in CBF correlated crudely with the duration of ischemia (r = -0.67, p less than 0.01). For CMRO2 correlation of the magnitude of decrease with the duration of ischemia was more evident (r = -0.74, p less than 0.001). Furthermore, the postischemic ratio of CBF to CMRO2 was virtually identical for all dog groups regardless of the ischemic time. The adequacy of the ratio of CBF to CMRO2 was reflected by adequate oxygen levels in the sagittal sinus blood of all dogs. The authors conclude that the delayed postischemic hypoperfusion state is probably not an important determinant of neuronal injury since its magnitude appears to be primarily determined by the metabolic needs of the brain.
J Cereb Blood Flow Metab 1990 Jan
PMID:Postischemic canine cerebral blood flow appears to be determined by cerebral metabolic needs. 229 38

Focal cerebral infarction and edema were measured in rats (Wistar, Fisher 344, and spontaneously hypertensive strains) pretreated with nimodipine (2 micrograms/kg/min i.v.) or its vehicle and subjected to the tandem occlusion of the middle cerebral and common carotid arteries. Animals awoke from anesthesia 10-15 min after onset of ischemia and continued to receive treatment over a 24-h survival period. Cortical infarction and edema were quantified by image analysis of frozen brain sections processed for histology. Nimodipine-treated rats developed 20-60% smaller cortical infarct volumes than controls (p less than 0.002). Cortical edema was reduced proportionately to the decrease in infarct volume and constituted approximately 36% of the infarct volume. Nimodipine caused a mild hypotensive response that did not aggravate ischemic brain damage. The results indicate that continuous nimodipine treatment, started before induction of focal cerebral ischemia, can attenuate ischemic brain damage and edema as late as 24 h after the onset of ischemia.
J Cereb Blood Flow Metab 1990 Jan
PMID:Continuous nimodipine treatment attenuates cortical infarction in rats subjected to 24 hours of focal cerebral ischemia. 229 39

The effects of the novel dihydronaphthyridine Ca2+ antagonist CI-951 on focal cerebral ischemia were assessed during MCA occlusion in 30 white New Zealand rabbits under 1.0% halothane anesthesia. In vivo brain pHi and focal CBF were measured with umbelliferone fluorescence. Baseline normocapnic brain pHi and CBF were 7.02 +/- 0.02 and 48.4 +/- 2.9 ml/100 g/min, respectively. In the severe ischemic regions, 15 min postocclusion brain pHi and CBF were 6.62 +/- 0.04 and 14.4 +/- 0.7 ml/100 g/min in controls vs. 6.60 +/- 0.02 and 12.9 +/- 2.3 ml/100 g/min, respectively, in animals destined to receive CI-951. Twenty minutes after MCA occlusion, CI-951 was administered at 0.5 microgram/kg/min and brain pHi and CBF were determined in both regions of severe and moderate ischemia for 4 h postocclusion. Control severe ischemic sites demonstrated no significant improvement in brain pHi and only mild increases in CBF over the next 4 h. CI-951 caused significant improvement in both of these parameters. Postocclusion 4 h brain pHi and CBF measured 6.69 +/- 0.04 and 18.5 +/- 3.2 ml/100 g/min in controls vs. 7.01 +/- 0.04 and 41.7 +/- 5.3 ml/100 g/min, respectively, in CI-951 animals (p less than 0.001). Similar improvements were observed in moderate ischemic sites. In animals that demonstrated postocclusion EEG attenuation, 75% of CI-951 animals had EEG recovery as compared to 18% in controls. CI-951 may be a useful therapeutic agent for focal cerebral ischemia if histological and outcome studies verify these data.
J Cereb Blood Flow Metab 1990 Jan
PMID:The novel dihydronaphthyridine Ca2+ channel blocker CI-951 improves CBF, brain pHi, and EEG recovery in focal cerebral ischemia. 229 40

The effect of unilateral, incomplete cerebral ischemia on CBF, unidirectional flux of alpha-aminoisobutyric acid (AIB) and sodium, and number of perfused capillaries during ischemia and reperfusion was measured in the cortex of gerbils with symptomatic ischemia. Three hours of unilateral carotid occlusion reduced the CBF to the ipsilateral cortex by 81%, with a smaller 30% decrease in the contralateral cortex. Following 11 min of reperfusion, CBF in the ipsilateral cortex returned to the preischemic value, while the contralateral blood flow decreased to 50% of control. The transfer constants for AIB and sodium in the ipsilateral cortex were reduced by 67 and 53%, respectively, after 3 h of ischemia, with no change in the contralateral cortex. The transfer constant for AIB remained decreased by 48% during the first 20 min of reperfusion, while that for sodium returned to its control value. The number of perfused capillaries was reduced 54% by 3 h of ischemia and remained decreased by 20% after 11 min of reperfusion. These data indicate that 3 h of unilateral carotid occlusion reduces the number of perfused capillaries in the ipsilateral cortex during the ischemic period. Further, the early reperfusion phase is characterized by a mismatch between capillary perfusion and CBF. Finally, early in the postischemic phase, sodium transport undergoes a selective stimulation, probably as a result of stimulation of ion transport.
J Cereb Blood Flow Metab 1990 Mar
PMID:Decrease in perfusion of cerebral capillaries during incomplete ischemia and reperfusion. 230 37


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