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

In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia, 12 pigtail monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p greater than 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors concluded that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.
J Cereb Blood Flow Metab 1987 Jun
PMID:Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates. 358 69

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1987 Oct
PMID:Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs. 365 2

Red blood cell concentration and hematocrit were assessed in the blood flowing in the capillaries of rabbit cerebral cortex (in unstained histologic sections prepared after in situ fixation of the tissue) and in the blood samples taken from the respective veins using direct, quantitative techniques. The values appeared to be significantly higher in veins than in capillaries under control conditions. With the development of cerebral ischemia, when the blood flow in the cortex was reduced to almost half of the control level, red cell concentration and hematocrit in the blood were found to decrease markedly both in the capillaries and veins of the brain, while in the femoral veins of the same animals the values remained essentially unchanged.
J Cereb Blood Flow Metab 1987 Dec
PMID:Hematocrit in cerebral capillaries and veins under control and ischemic conditions. 369 29

Mitochondrial degradation is implicated in the irreversible cell damage that can occur during cerebral ischemia and reperfusion. In this study, the effects of 10 min of ventricular fibrillation and 100 min of spontaneous circulation on brain mitochondrial function was studied in dogs in the absence and presence of pretreatment with the Ca2+ antagonist lidoflazine. Twenty-three beagles were separated into four experimental groups: (i) nonischemic controls (ii) those undergoing 10-min ventricular fibrillation, (iii) those undergoing 10-min ventricular fibrillation pretreated with 1 mg/kg lidoflazine i.v., and (iv) those undergoing 10-min ventricular fibrillation followed by spontaneous circulation for 100 min. Brain mitochondria were isolated and tested for their ability to respire and accumulate calcium in a physiological test medium. There was a 35% decrease in the rate of phosphorylating respiration (ATP production) following 10 min of complete cerebral ischemia. Those animals pretreated with lidoflazine showed significantly less decline in phosphorylating respiration (16%) when compared with nontreated dogs. Resting and uncoupled respiration also declined following 10 min of fibrillatory arrest. One hundred minutes of spontaneous circulation following 10 min of ventricular fibrillation and 3 min of open-chest cardiac massage provided complete recovery of normal mitochondrial respiration. Energy-dependent Ca2+ accumulation by isolated brain mitochondria was unimpaired by 10 min of complete cerebral ischemia. However, by 100 min after resuscitation, there was a small, but significant rise in the capacity for mitochondrial Ca2+ sequestration when compared to either control or fibrillated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1987 Dec
PMID:Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine. 369 30

An experimental model for repeated ischemic attacks, which allows easy induction of cerebral ischemia of any desired duration and frequency, has been developed in the gerbil. With this procedure, a pronounced cumulative effect on development of edema and tissue injury was observed using 3 separate, 5-min bilateral occlusions of the common carotid arteries spaced at various time intervals. This effect was most evident when the occlusions were carried out at 1-h intervals, i.e., during the period of marked postischemic hypoperfusion. Such animals, killed after 24 h of recirculation, showed significantly more severe edema and brain tissue injury in the areas exposed to ischemia than was observed in animals killed 24 h after single 5- or 15-min occlusions. The changes of regional CBF, assayed with a [3H]nicotine method, indicated a relatively rapid onset of hypoperfusion of similar degree after each release of arterial occlusion. The hypoperfusion recovered significantly within 6 h of recirculation following either single or multiple occlusions, and no residual hypoperfusion was observed in animals which, when killed at 24 h, showed severe edema and brain tissue injury. This model should prove useful in elucidating the pathophysiological mechanisms operative in repetitive cerebral ischemia.
J Cereb Blood Flow Metab 1987 Dec
PMID:Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults. 369 33

1,3-Butanediol (BD) is converted in the body to beta-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia. The aim of this study was to determine if BD would reduce brain damage following cerebral ischemia. A transient forebrain ischemia of 30-min duration was induced by the four-vessel occlusion technique in control and BD-treated rats (25 mmol/kg, i.p.; 30 min prior to ischemia). BD treatment led to significant improvement of neurologic deficit during the 72-h recovery period and reduced neuronal damage in the striatum and cortex but not in the CA1 sector of the hippocampus. Evaluation of cerebral energy metabolism before and at the end of the ischemic period showed that the treatment did not change the preischemic glycolytic and energy metabolite levels but attenuated the ischemia-induced metabolic alterations. It increased energy charge, phosphocreatine, and glucose levels, and reduced lactate accumulation. The decrease in brain lactate concentration might account for the beneficial effects of BD by minimizing the neuropathological consequences of lactic acidosis.
J Cereb Blood Flow Metab 1987 Dec
PMID:Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study. 369 36

Alterations in the regional CBF after occlusion of the posterior communicating, middle cerebral, or common carotid artery were investigated in the gerbil with a quantitative autoradiographic technique using [14C]iodoantipyrine. Occlusion of the posterior communicating artery produced severe ischemia in the ipsilateral hippocampus, thalamus, and dorsal mesencephalon. Occlusion of the middle cerebral artery produced severe ischemia in the ipsilateral rostral and central cerebral cortex and lateral caudate-putamen. Occlusion of the common carotid artery produced ipsilateral hemispheric ischemia of variable degrees. The distribution and degree of cerebral ischemia produced by occlusion of one of these arteries correlated closely to the arterial territory and the extent of collateral blood supply. Since the areas affected after occlusion of the posterior communicating or middle cerebral artery differ, those models will be useful for the comparative investigation of the ischemia-related cerebral pathophysiology associated with different sites of primary lesion.
J Cereb Blood Flow Metab 1986 Jun
PMID:Regional cerebral ischemia in the gerbil: measurement of regional cerebral blood flow by quantitative autoradiography. 371 Nov 62

Focal cerebral ischemia was induced in rats by occlusion of the middle cerebral artery. By a triple-tracer technique, cerebral glucose utilization, glucose content, and blood flow were simultaneously determined. Computer-assisted autoradiography revealed a core of dense ischemia in the lateral two-thirds of the striatum. A border zone of increased 2-deoxy-D-glucose (DG) uptake surrounded the ischemic insult in the acute stage. The lumped constant was increased only moderately in the border zone. Therefore, the enhanced DG uptake reflected increased glucose consumption. CBF was reduced to 20-30% in the cortical border, while minor depression and in some animals hyperemia were evident in the striate border. Six hours after the insult, the border zones of increased glucose consumption had disappeared in half the animals. In no animals examined after 20 h was glucose consumption enhanced. The study indicated a stable metabolic response to a reproducible focal insult. We conclude that continued enhancement of glucose consumption in marginally perfused areas indicates neuronal damage.
J Cereb Blood Flow Metab 1986 Aug
PMID:Focal ischemia of the rat brain: autoradiographic determination of cerebral glucose utilization, glucose content, and blood flow. 373 1

The effects of cerebral ischemia on perineuronal glia were studied in the rat model of transient four-vessel occlusion. Striatum containing irreversibly injured neurons and paramedian cerebral cortex containing reversibly injured neurons were prepared for electron microscopy at intervals of 3 min up to 24 h following ischemia. Perineuronal astrocytes showed cytoplasmic swelling and configurational changes in and pleomorphism of mitochondria similar to those described previously in parenchymal astrocytes in this model. Dark oligodendroglia showed only transient swelling of cisterns of Golgi apparatus and endoplasmic reticulum. However, medium-light oligodendrocytes significantly increased in size and accumulated microtubules and tubovesicular profiles in the cytoplasm. Reactive glia with features of both oligodendrocytes and astrocytes appeared at 15 min. A sharp drop in the number of perineuronal medium-light oligodendrocytes occurred at 3 h after ischemia and was accompanied by increased numbers of astrocytes and intermediate glia. Cortical glia showed similar changes that were milder and reversible. These studies suggest that certain perineuronal glia are transformed into reactive astrocytes in areas of ischemic neuronal necrosis, although current data are insufficient to determine if the transforming cells are astrocytes, light oligodendrocytes, or intermediate glia. Possible stimuli for these glial reactions include loss of or changes in neuronal trophic factors upon CNS glia or alterations in the interstitial fluid composition.
J Cereb Blood Flow Metab 1986 Oct
PMID:Transformation of postischemic perineuronal glial cells. I. Electron microscopic studies. 376 46

The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10(-11)-10(-3) M), H+ (pH 5.1-7.6), or K+ (0-10 mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.
J Cereb Blood Flow Metab 1986 Dec
PMID:Effect of gamma-hydroxybutyrate on the reactivity of pial arteries before and after ischemia. 379 1


<< Previous 1 2 3 4 5 6 7 8 9 10