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

The effects of flunarizine on local cerebral blood flow, cortical energy metabolism and neuronal necrosis were evaluated in a rat model of forebrain ischemia. The application of flunarizine (2 X 40 mg/kg p.o.) at 24 and 4 h before ischemia accelerated the restoration of cortical high-energy phosphates during early post-ischemic recirculation and also increased the flow in cortical but not in hippocampal areas. Neuronal necrosis was reduced in the hippocampal CA 1 sector but unchanged in the cortex. It is concluded that flunarizine reduces ischemic damage mainly via a direct effect on brain tissue.
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PMID:Effects of flunarizine on postischemic blood flow, energy metabolism and neuronal damage in the rat brain. 325 1

Spontaneous and sinusoidal-evoked nerve activity in semicircular canal afferent fibers of the bullfrog was evaluated prior to and following the production of ischemia of the labyrinthine arterial supply by mechanical occlusion of the vestibular artery. Neuronal spontaneous firing rates were observed to diminish by up to 100% within 10 min following the onset of ischemia. In most neurons there was a substantial increase in firing rate during the first few minutes. The sensitivity of the fibers to natural stimulation as determined by the gain in their responses to sinusoidal motion also diminished by as much as 75% over the same period. No detectable changes in the membrane potentials of the neurons were observed. The changes in excitability were closely correlated with the changes in spontaneous firing rate, but not all the neurons whose responses changed showed changes in spontaneous activity. Likewise, the relative magnitude of change varied from neuron to neuron.
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PMID:Differential effect of ischemia on spontaneous and sinusoidal-evoked activity in semicircular canal afferents in the bullfrog. 349 Jul 31

The influence of transient forebrain ischemia on adenosine A1 and muscarinic cholinergic receptors in the gerbil brain 1-27 days after recirculation was studied. The topographical distribution and the alteration in the adenosine A1 and muscarinic receptor sites were analyzed by means of quantitative receptor autoradiography using [3H]cyclohexyladenosine ([3H]CHA) and [3H]quinuclidinyl benzilate ([3H]QNB), respectively. In most regions examined, the temporal profiles of the alteration of the receptor density were in accordance with the histopathological findings. [3H]CHA binding activity decreased suddenly after neuronal damage, while [3H]QNB grain density showed a gradual decrease in the dorsolateral caudate-putamen and in the CA1 subfield of the hippocampus. In the caudate-putamen, [3H]CHA and [3H]QNB binding activity in the dorsal aspect was markedly reduced 1-27 days after ischemia. [3H]CHA binding activity in the ventromedial region of the caudate-putamen also decreased 1-3 days after ischemia, though neuronal damage was restricted to the dorsolateral aspect. Neuronal death in CA1 was preceded by the decrease in [3H]QNB binding activity in the stratum radiatum 1 and 2 days after ischemia. Marked decrease in [3H]QNB and [3H]CHA binding activity was noted in the CA1 subfield 3-27 days after recirculation. Three to 27 days after ischemia, the A1 binding activities in the CA3 subfield of the hippocampus and in the dentate gyrus were reduced despite the normal appearance of these areas throughout the reperfusion period. Muscarinic binding sites in the CA3 subfield were also reduced 27 days after ischemia. Despite minimal neuronal damage in the lateral septal nucleus and in the substantia nigra, the A1 binding activity in these regions was reduced by 70% and 50%, respectively. These results provide further evidence that the muscarinic receptors in the dorsolateral region of the caudate-putamen are localized postsynaptically on small and medium-sized neurons and that those in the CA1 subfield of the hippocampus are localized on the CA1 pyramidal cells.
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PMID:Quantitative autoradiographic analysis of muscarinic cholinergic and adenosine A1 binding sites after transient forebrain ischemia in the gerbil. 360 99

An in vitro system was used to mimic several aspects of ischemia, including low oxygen pressure, low nutrient levels, and the accumulation of cellular products thought to contribute to damage during ischemia. We replaced normal culture medium from 3-week-old basal ganglia cultures with oxygen-depleted, nutrient-deficient medium. After incubation in an atmosphere of 94% N2, 6% CO2 for 5 hr at 37 degrees C, the cultures were returned to normal medium. After a 24 hr recovery period, cell viability was assessed in terms of cell number, electrophysiological properties, and immunohistochemical markers. When the medium used during the ischemic period was a normal balanced salt solution, more than 70% of the cells were damaged by the low-oxygen, low-glucose stress. Loss of cell processes and cell swelling were the most evident signs of damage. The majority of the cells remaining viable were astrocytes. Neuronal damage was observed only when both glucose and oxygen were deficient. Some damage was evident even at oxygen tensions of 60 mm Hg when glucose was absent from the medium; much more extensive damage was observed at tensions below 1.0 mm Hg. Lowering both extracellular sodium and calcium resulted in more than a 2-fold increase in survival (70 vs 28%). These results indicate that damage to neurons during conditions of extreme energy deprivation such as ischemia may be mediated by the influx of calcium and/or sodium.
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PMID:Effects of ischemia-like conditions on cultured neurons: protection by low Na+, low Ca2+ solutions. 377 25

Cats were submitted to complete cerebral ischemia by clamping the innominate and subclavian arteries and simultaneously lowering the systemic blood pressure. Neuronal function was assessed by recording the electroencephalogram and the anti- and orthodromic activation of the pyramidal tract. A full recovery of the pyramidal response and even of evoked electroencephalographic activity occurred after ischemia of more than 1 hour's duration.
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PMID:Recovery of neuronal function after prolonged cerebral ischemia. 490 37

Rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. After recovery with glucose, they were allowed to wake up and survive for 1 week. Control rats were recovered at the stage of EEG slowing. After sub-serial sectioning, the number and distribution of dying neurons was assessed in each brain region. Acid fuchsin was found to stain moribund neurons a brilliant red. Brains from control rats showed no dying neurons. From 10 to 60 min of cerebral isoelectricity, the number of dying neurons per brain correlated positively with the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min. Neuronal necrosis was found in the major brain regions vulnerable to several different insults. However, within each region the damage was not distributed as observed in ischemia. A superficial to deep gradient in the density of neuronal necrosis was seen in the cerebral cortex. More severe damage revealed a gradient in relation to the subjacent white matter as well. The caudatoputamen was involved more heavily near the white matter, and in more severely affected animals near the angle of the lateral ventricle. The hippocampus showed dense neuronal necrosis at the crest of the dentate gyrus and a gradient of increasing selective neuronal necrosis medially in CA1. The CA3 zone, while relatively resistant, showed neuronal necrosis in relation to the lateral ventricle in animals with hydrocephalus. Sharp demarcations between normal and damaged neuropil were found in the hippocampus. The periventricular amygdaloid nuclei showed damage closest to the lateral ventricles. The cerebellum was affected first near the foramina of Luschka, with damage occurring over the hemispheres in more severely affected animals. Purkinje cells were affected first, but basket cells were damaged as well. Rare necrotic neurons were seen in brain stem nuclei. The spinal cord showed necrosis of neurons in all areas of the gray matter. Infarction was not seen in this study. The possibility is discussed that a neurotoxic substance borne in the tissue fluid and cerebrospinal fluid (CSF) contributes to the pathogenesis of neuronal necrosis in hypoglycemic brain damage.
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PMID:The distribution of hypoglycemic brain damage. 649 35

Thirty-eight male Wistar rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. Plasma glucose levels during cerebral isoelectricity ranged from 0.12 mM to 1.36 mM. Control rats were injected with insulin, but hypoglycemia was terminated with glucose at the stage of large delta-wave EEG slowing. After recovery, the rats were allowed to wake up and survive for 1 wk. The number of dying neurons was assessed with acid-fuchsin/cresyl-violet-stained, whole-brain, subserial sections using direct visual counting of acidophilic, cytoclastic neurons. Brains from control rats that were not allowed to become isoelectric showed no dying neurons. Ten minutes of cerebral isoelectricity produced very minimal brain damage. The density of neuronal necrosis was positively related to the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min, but showed no correlation with the blood sugar levels. The cerebral cortex, hippocampus, caudate nucleus, spinal cord, and, to a lesser extent, cerebellar Purkinje cells were affected. The distribution of neuronal necrosis was not identical with that seen in ischemia, but, rather, suggested a CSF-borne neurotoxin operant in contributing to the pathogenesis of neuronal necrosis in hypoglycemic brain damage. Neuronal death does not occur in hypoglycemia unless the EEG becomes isoelectric, whatever the blood sugar level. Serious brain damage does not occur until electrocerebral silence has been established for at least several minutes. Neuronal death accelerates after 30 min of EEG isoelectricity in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study. 650 Jan 89

Electron microscopy of the sensomotor cortex in 27 rats was performed at varying times (1, 3, 7 days) after arteria carotis communis occlusion. Three groups of rats (5 rats in every group) were treated by nootropil (500 mg/kg daily) in accordance with three time intervals. Control rats were undrugged. More preserved were neurons in the brain of rats treated by nootropil. Neuronal organelles had rare signs of irreversible damages. Membranes were more often preserved, organelles fragmentation and vacuolization were less pronounced. The experimental rats showed neurons containing numerous ribosomes and small new-formed mitochondria. The difference in neuronal structure in treated and untreated rats became more distinct 3-7 days after occlusion. The results obtained are suggested to be connected with the drug ability to normalize ATP metabolism, to stimulate phospholipid synthesis and ribosome function and to increase glucose utilization. The problem of using GABA derivatives in conditions of the most acute brain ischemia is discussed.
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PMID:[Ultrastructural aspects of acute cerebral ischemia during nootropil administration (experimental study)]. 662 31

Neuronal lesions in the brain occur in conditions associated with a reduced supply of oxygen (hypoxia and ischemia) and glucose (hypoglycemia) as well as in those associated with a pathologically enhanced neuronal activity (status epilepticus). In only two of these conditions (hypoxia and ischemia) are the lesions correlated to cellular oxygen lack, and gross energy failure is absent in one condition (status epilepticus). Although anaerobic mechanisms seem responsible for the cell injury in hypoxia and ischemia, oxidative mechanisms could operate in hypoglycemia and status epilepticus. Since the supply of oxygen has not ceased altogether in hypoxia and incomplete ischemia, and since reoxygenation/recirculation leads to a transient increase in tissue oxygen tensions, one cannot exclude the possibility that oxidative mechanisms contribute to the final damage following all types of cellular oxygen lack. We have failed to obtain evidence that peroxidative degradation of cellular constituents occurs in hypoglycemia and status epilepticus. Thus, there is neither a perturbation of the redox state of the glutathione pool of the tissue nor a measurable degradation of polyenoic phospholipid-bound fatty acids. It is emphasized that the cascade of events triggered by an accumulation of free polyenoic fatty acids, mainly arachidonic acid, may contribute to cell lesions by leading to cell edema and/or microcirculatory changes. During seizures, such an accumulation occurs even though energy failure is moderate and it may conceivably contribute to cell damage. In general, though, mechanisms of cell damage in the brain remain partly elusive.
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PMID:Neuronal cell damage in the brain: possible involvement of oxidative mechanisms. 693 2

In vitro ischemia models have utilized oxygen, or oxygen and glucose deprivation to simulate ischemic neuronal injury. Combined oxygen and glucose deprivation can induce neuronal damage which is in part mediated through NMDA receptors. Severe oxygen deprivation alone however can cause neuronal injury which is not NMDA mediated. We tested the hypothesis that NMDA, or non-NMDA receptor mediated mechanisms may predominate, to induce neuronal injury following severe oxygen deprivation depending on the presence of glucose. We found that NMDA receptor blockade using dizocilpine (MK-801), DL-2-amino-5-phosphonovaleric acid (APV), or CGS 19755, was highly effective in reducing CA1 injury in organotypic hippocampal cultures, caused by complete oxygen and glucose deprivation. Complete oxygen deprivation alone however, caused CA1 neuronal injury which was not diminished using NMDA receptor blockade alone with MK-801 or APV, or in combination with AMPA/kainate receptor blockade using 6-cyano-7-dinitroquinoxalone-2,3-dione (CNQX). Neuronal protective strategies which act primarily through non-glutamate dependent mechanisms, including hypothermia, low chloride and calcium, and the free radical scavenger, alpha-phenyl-tert-butyl nitrone (PBN), provided neuronal protection against complete oxygen, as well as combined oxygen/glucose deprivation. Raising the pH using Hepes buffer during complete oxygen deprivation did not result in neuronal protection by NMDA receptor blockade. Partial oxygen deprivation alone, partial oxygen deprivation combined with glucose deprivation, glucose deprivation alone, and also glutamate exposure, all produced neuronal damage that was reduced by NMDA receptor blockade. The presence of glucose during complete oxygen deprivation appears to prevent glutamate receptor blockade from reducing neuronal injury in organotypic hippocampal cultures.
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PMID:Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures. 747 21


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