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

We have examined the effect of cortical spreading depression (SD) and anoxic depolarization (AD) on the interstitial concentration changes of amino acids (AA) in the neocortex of anesthetized rats using microdialysis and HPLC. Accompanying SD alanine increased to 126 +/- 11%, arginine to 116 +/- 3%, aspartate to 160 +/- 17%, glutamate to 163 +/- 9%, glycine to 158 +/- 21%, serine to 125 +/- 9%, and taurine to 172 +/- 15% (mean +/- 1 S.E.M.). The increases lasted for about 1 min. Histidine decreased to 74% +/- 4% at 1 min following SD, and returned to normal 4 min later. Cardiac arrest triggered AD after approximately 2 min, immediately followed by changes of interstitial AAs. At 5 min after AD alanine had increased to 183 +/- 13%, aspartate to 3,458 +/- 656%, GABA to 338 +/- 35%, glutamate to 1,696 +/- 546%, glycine to 297 +/- 37%, serine to 153 +/- 12%, and taurine to 1721 +/- 98% as compared to control values (mean +/- 1 S.E.M.). Histidine decreased to 78 +/- 2% at 3 min following AD while arginine exhibited insignificant variations around the baseline. The increase of glutamate during SD is consistent with activation of NMDA-receptors as an essential requirement for this reaction. The increase of AAs may also contribute to the sequence of events leading to AD, though the exact mechanism remains unknown. SD is an important pathophysiological mechanism of the ischemic penumbra associated with focal cerebral ischemia, while AD reflects the electrophysiological status of the infarct core.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. 833 Feb 14

The damaging effects from transient forebrain ischemia may be a result of excessive excitability or loss of inhibitory influences. In the brain, GABA acts as the major inhibitory neurotransmitter and its loss may be an important factor leading to delayed neuronal damage in the substantia nigra reticulata (SNr). In this study, we looked at the protective effects of muscimol, a GABA A agonist in a gerbil model of repetitive forebrain ischemia. For cerebral ischemia, we used three episodes of 2 min with a reperfusion period of 1 h between the insults. Histological evaluations were done 7 days after the insult using silver degeneration staining. Muscimol was infused into the third ventricle continuously for 7 days beginning just prior to the insult. There were a total of 20 animals, 12 treated with muscimol and the other 8 serving as controls. At 7 days, there was significant protection in the cortex (P = 0.007), hippocampus [CA1 (P = 0.01), CA4 (P = 0.015)], substantia nigra reticulata (P = 0.007), striatum (P = 0.049), and thalamus (P = 0.012). All statistical comparisons were done using nonparametric tests (Mann-Whitney U test). Our study shows that potentiation of inhibitory mechanisms may be important mechanisms of neuronal protection from the effects of repetitive ischemia and the effects are not limited to the SNr. Further studies are needed to better understand their mechanism of action.
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PMID:GABA agonist "muscimol" is neuroprotective in repetitive transient forebrain ischemia in gerbils. 840 90

The effects of a 20 min period of four-vessel occlusion cerebral ischemia followed by reperfusion on glutamate, aspartate, GABA and glycine efflux from the rat cerebral cortex were studied using a cortical cup technique. Cerebral ischemia increased amino acid concentrations in the cortical superfusates. When the cerebral cortices were exposed to topically applied GM1 ganglioside (50 microM) for 40 min prior to ischemia, the evoked efflux of all four amino acids was significantly inhibited. GM1 (1 microM) failed to inhibit amino acid release. The results support the concept that gangliosides have a cerebroprotective action.
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PMID:GM1 ganglioside inhibits ischemic release of amino acid neurotransmitters from rat cortex. 858 Apr 29

In acute experiments on anesthetized cats with cerebral ischemia in conditions of autohemoperfusion of cerebral and peripheral vessels with a stable volume of blood we found that lithium oxybutirate and new GABA derivatives: LOS 1-84 and LOS 5-79 affect the cerebral blood flow and metabolism in the brain. Prophylactic intravenous injection of lithium oxybutirate did not affect the development of postischemic hyperperfusion but inhibited postischemic hyperperfusion. The compounds prevent the development of postischemic phenomena and promote the recovery of metabolism in the brain.
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PMID:[The effect of lithium derivatives of GABA on blood circulation and metabolic indices in the brain under ischemia]. 870 81

In order to investigate changes in levels of monoamines and their related substances together with those of other neurotransmitters (acetylcholine and GABA), choline and substances related to energy metabolism (ATP, lactate and glucose) accompanying incomplete cerebral ischemia, a bilateral common carotid artery occlusion model of spontaneously hypertensive rats (SHR) was utilized. Animals were subjected to 1 or 2 h ischemia. Then the concentrations of substances were measured in the cerebral cortex, hippocampus and striatum and compared with control values. Due to the incomplete ischemia, ATP showed a moderate decrease, while lactate and choline increased remarkably, and GABA underwent a moderate increase. With regard to monoamines, both noradrenaline and serotonin levels were reduced in the cerebral cortex and hippocampus, whereas dopamine levels increased in the hippocampus. All monoamine metabolites, i.e. metabolites by monoamine oxidase (MAO), metabolites by catechol-O-methyltransferase (COMT), and metabolites by both MAO and COMT, underwent increases. The 3-methoxytyramine level in particular showed marked increases. Furthermore levels of precursor amino acids as well as 5-hydroxytryptophan rose. Acetylcholine decreased moderately only in the cerebral cortex. Among these changes, sustained increases in all the monoamine metabolites were characteristic of changes in the incompletely ischemic brain, suggesting that both COMT and MAO retain their activities in the incompletely ischemic brain.
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PMID:Changes in levels of monoamines and their metabolites in incompletely ischemic brains of spontaneously hypertensive rats. 878 4

The effect of the kappa-opioid agonist enadoline (CI-977) upon the relationship between cerebral blood flow and glutamate release was simultaneously assessed (using microdialysis and hydrogen clearance techniques respectively) at the same anatomical locus in the cerebral cortex (suprasylvian gyrus) after permanent middle cerebral artery (MCA) occlusion in halothane-anaesthetised cats. During controlled graded ischaemia, pretreatment with enadoline (0.3 mg/kg i.v. followed by continuous infusion at 0.15 mg/kg/h), initiated 30 min prior to MCA occlusion, significantly attenuated the marked increases in extracellular glutamate, aspartate and GABA observed in the focal ischaemic penumbra. The present data are consistent with the hypothesis that the neuroprotective efficacy of enadoline in focal cerebral ischaemia is due to inhibition of glutamate release in the ischaemic penumbra.
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PMID:The relationship between glutamate release and cerebral blood flow after focal cerebral ischaemia in the cat: effect of pretreatment with enadoline (a kappa receptor agonist). 881 9

Enhancing inhibitory mechanisms has been shown to improve neuronal survival after transient focal or global ischemia. In most studies, histological evaluations have been confined to the CA1 region of the hippocampus up to 7 days after an ischemic insult. We have previously shown that continuous intra-ventricular infusion of gamma-vinyl GABA (GVG) results in significant protection after cerebral ischemia. This present study was designed to assess histological and behavioral function at 7 and 28 days after a single 5 min ischemic episode in gerbils. One set of animals received the medication 30 min before the insult and the other set at 1 h after the insult. Evaluation at 7 days showed significant protection in most regions of the brain in both the pre- and post-ischemic treated animals in comparison to the controls. Delayed evaluation at 28 days showed significant protection only in the pre-ischemic treated animals. Behavioral testing with Morris water maze showed no differences in either pre- or post-ischemic treated animals when compared to saline-treated ischemic controls. Our study clearly demonstrates the usefulness of delayed evaluation in the assessment of 'true' neuronal protection. Pre-ischemic treated animals showed persistent and true neuronal protection, in contrast to a temporary protection as seen at 7 days in the post-ischemic treated animals. The lack of behavioral improvement in the pre- and post-ischemic treated animals suggests that morphological protection alone cannot be considered as the sole criterion for successful outcome.
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PMID:The neuroprotective effects of gamma-vinyl GABA in transient global ischemia: a morphological study with early and delayed evaluations. 892 63

Previously, we showed that arachidonic acid and prostaglandin metabolites inhibited GABAA responses in rat cerebral cortex. Thromboxane A2 (TXA2), a metabolite of arachidonic acid, has potent actions on blood vessels and platelets, but its actions on neurons are not known. Here, we examined the effects of several TXA2 analogs on the functional and binding characteristics of GABAA receptors in rat brain. The stable analogs of TXA2, pinane and carbocyclic TXA2, and the TXA2 agonist, U-46619, inhibited muscimol-induced 36Cl- uptake in cerebral cortical synaptoneurosomes. Carbocyclic TXA2 decreased the maximal response to muscimol, consistent with a non-competitive interaction. The TXA2 antagonist, SQ 25,548, did not block the effects of either arachidonic acid or carbocyclic TXA2. Neither the biologically inactive metabolite of TXA2, TXB2, nor carbacyclin, a stable analog of prostacyclin (prostaglandin I2) had an effect on GABAA responses. Thus the pharmacology differs from that in vascular smooth muscle and platelets. To determine if GABAA receptors were sensitive to the thromboxanes, the effect of pinane TXA2 on the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to GABA-gated Cl- channels was measured using receptor autoradiography. Pinane TXA2 inhibited [35S]TBPS binding in a regionally selective and non-competitive manner; the greatest inhibition was in the cerebral cortex, hippocampus and striatum, areas which are selectively vulnerable to cerebral ischemia. We conclude that TXA2 can interact with neuronal membranes to inhibit GABA receptor function, independent of its actions on the cerebrovasculature and on glial cells. This may be important during pathologic states such as ischemia, when TXA2 accumulates in extracellular spaces.
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PMID:Inhibition of GABA-gated chloride channels in brain by the arachidonic acid metabolite, thromboxane A2. 901 51

Neuronal and glial cell swelling occurs rapidly in ischemia as part of the cytotoxic response. Astrocytic swelling is known to result in large extracellular increases in certain amino acids, including glutamate, aspartate and taurine, as part of the regulatory volume decrease (RVD) response inherent to these and other cells. RVD in astrocytic cultures is inhibited by anion channel blockers. In this study, we compared the effects of three anion channel blockers on the ischemia/reperfusion-evoked release of amino acids from the in vivo rat cerebral cortex. Twenty minutes of four vessel cerebral ischemia caused significant increases in cortical superfusate levels of aspartate, glutamate, GABA, taurine and phosphoethanolamine. During reperfusion there were delayed increases in the level of glycine, alanine and serine. Glutamine levels were not affected. Cl- channel blockers, 4-acetamido-4'-isothiocyanostrilbene-2,2'-disulfonic acid (SITS, 2 mM), 5-nitro-2-(3-phenyl-propylamino)benzoic acid (NPPB, 350 microM) and dipyridamole (200 microM) depressed basal releases of glutamate and taurine and the ischemia/reperfusion-evoked releases of aspartate, glutamate, taurine and phosphoethanolamine. The results suggest that diffusion of amino acids through an anion channel may be partially responsible for the elevated extracellular levels of excitotoxic and other amino acids that occur during cerebral ischemia/reperfusion.
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PMID:Inhibition by anion channel blockers of ischemia-evoked release of excitotoxic and other amino acids from rat cerebral cortex. 920 27

PNU-101017 is a novel, imidazoquinoline amide and benzodiazepine receptor partial agonist that has high affinity for the GABAA receptor subtypes containing the alpha 1 and alpha 3 or alpha 5 subunits. At each of these receptors, the compound is a partial agonist with approximately 50% of the intrinsic activity of the full agonist diazepam. In view of the previously demonstrated anti-ischemic effects of some GABA agonists, the purpose of this study was to determine the ability of PNU-101017 to salvage selectively vulnerable neuronal populations in the gerbil forebrain ischemia model. In an initial set of experiments, male gerbils were pretreated 30 minutes before ischemia induction (5 minutes) with PNU-101017 (3, 10, or 30 mg/kg intraperitoneally) and again 2 hours after reperfusion. In vehicle (0.05 N HC1)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 80%. PNU-101017 was shown to produce a dose-related increase in CA1 neuronal survival; at either 10 or 30 mg/kg, the loss of CA1 neurons was only 21% (P < 0.005 versus vehicle). A second experiment, examined the therapeutic window for PNU-101017 using the dose level of 30 mg/kg intraperitoneally. Administration of the first of two doses (2 hours apart) at the time of reperfusion resulted in an identical decrease in CA1 damage at 5 days to that seen with preischemic treatment (P < 0.003 versus vehicle). Even with a delay of the initial dosing until 4 hours after reperfusion, PNU-101017 reduced CA1 neuronal loss to only 32% (P < 0.01 versus vehicle). In a third experiment in which the duration of the ischemic insult was increased to 10 minutes and the brains were not analyzed until 28 days after ischemia, daily PNU-101017 dosing for the full 28 days still significantly preserved CA1 neurons, although less effectively than in the milder 5 minute-ischemia model. The loss of dopaminergic nigrostriatal neurons was also reduced. The neuroprotective effect of PNU-101017 was not associated with any overt CNS depression and it did not correlate with hypothermia. This benzodiazepine-receptor partial agonist may have potential for the treatment of global cerebral ischemia.
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PMID:Neuroprotective properties of the benzodiazepine receptor, partial agonist PNU-101017 in the gerbil forebrain ischemia model. 929 May 85


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