Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
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PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

Bilateral ischemia has been shown to alter the net brain levels of energy metabolites such as ATP, phosphocreatine, glucose, and glycogen. The amino acid neurotransmitter gamma-aminobutyric acid (GABA) exerts a tonic inhibitory influence on neural activity. The present studies were designed to evaluate the influence of elevated GABA levels on the metabolic sequelae of ischemia. The GABA transaminase inhibitor gamma-vinyl-GABA (GVG; vigabatrin) was administered to Mongolian gerbils before the production of a bilateral ischemic incident. GABA levels were elevated in all regions assayed. Levels of energy metabolites were also increased, an indication of reduced energy utilization. In control animals, in the absence of GVG, 1 min of bilateral ischemia produced decreases in the levels of all metabolites. In animals pretreated with GVG, the effects of 1 min of bilateral ischemia were attenuated. These data suggest that the level of ongoing activity may affect the response to an ischemic insult. Furthermore, GVG may have a clinical indication in reducing the effect of minor ischemic incidents.
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PMID:Elevated gamma-aminobutyric acid levels attenuate the metabolic response to bilateral ischemia. 149 8

Excitatory amino acids (EAAs) have been implicated to play a part in the development of hypoxic-ischemic brain injury in the neonate. The aim of the present study was to follow changes of intra- and extracellular (microdialysis) amino acids in the cerebral cortex in a model where cortical hypoxic-ischemic damage is produced consistently. Hypoxic-ischemia (unilateral ligation of the carotid artery + 2 h of exposure to 7.8% oxygen) caused a depletion of tissue ATP, phosphocreatine and glucose with a concomittant accumulation of AMP and lactic acid in cortical tissue. These changes were accompanied by a decrease of tissue aspartate and glutamine whereas the contents of gamma-aminobutyric acid (GABA), phenylalanine, leucine, isoleucine, valine and alanine increased. In the extracellular fluid GABA, glutamate, aspartate, taurine, glycine and alanine all increased multi-fold during hypoxic-ischemia. Aspartate and glutamate returned to near initial levels 2 h after the end of the insult, whereas the elevation of glycine persisted during recovery. In conclusion, the high extracellular levels of EAAs and glycine may exert injurious effects during and after hypoxic-ischemia.
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PMID:Intra- and extracellular changes of amino acids in the cerebral cortex of the neonatal rat during hypoxic-ischemia. 178 36

Neuronal vulnerability to ischemia in the rat hippocampus was investigated by the measurement of high potassium evoked overflow of neurotransmitters using in vivo microdialysis. Changes in the extracellular level of amino acids caused by high potassium (100 mM) stimulation were measured on the 5th day after 20 min of forebrain ischemia, and the ratio of stimulated to basal levels or the peak concentration following the stimulation were correlated to neuronal activities. The responses to high potassium stimulation of glutamate and aspartate were reduced to 35-40% of the control values on the 5th day after 20 min ischemia, whereas the responses of gamma-aminobutyric acid (GABA) and taurine were not reduced on the 5th day after the ischemia. These results suggest that excitatory amino acid neurons (glutamatergic and aspartatergic) are more vulnerable than inhibitory amino acid neurons (GABAergic and taurinergic) in the hippocampus. Histologically, hippocampal CA1 pyramidal cells, which are believed to be glutamatergic or aspartatergic, demonstrated a marked neuronal necrosis on the 5th days after 20 min ischemia. Biochemical features revealed by high potassium stimulation may be an expression of 'delayed neuronal death' in the hippocampal CA1 area.
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PMID:Ischemic neuronal injury in the rat hippocampus following transient forebrain ischemia: evaluation using in vivo microdialysis. 190 77

Excitatory amino acids (EAAs) have been implicated in the pathophysiology of cellular injury after brain ischemia. Changes in extracellular levels of amino acids in rat cerebral cortex after permanent proximal middle cerebral artery (MCA) occlusion were examined using microdialysis. Significant increases were found in dialysate concentrations of glutamate, aspartate and gamma-aminobutyric acid (GABA) from the ischemic cortex during the first 90 min after MCA occlusion compared to pre-ischemic concentrations and contralateral hemispheric controls. Total tissue levels of these amino acids in the infarcted hemisphere 90 min after onset of ischemia were not different from the contralateral hemisphere. These results are consistent with the hypothesis that the release of EAAs may contribute to tissue damage in focal cerebral ischemia.
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PMID:Changes in extracellular amino acid neurotransmitters produced by focal cerebral ischemia. 197 Jan 40

In the present study we investigated the relative vulnerability of neuronal subsets in the striatum to ischemia that was induced by bilateral transient ligation of the common carotid arteries in gerbils. After 4 days of survival, brains were evaluated using histochemical methods (NADPH-diaphorase and silver degeneration procedures) and neurochemical methods with radioimmunoassays for somatostatin-, neuropeptide Y-, and substance P-like immunoreactivity and measurements of amino acids using high-pressure liquid chromatography with electrochemical detection. NADPH-diaphorase-positive neurons were strikingly preserved in the ischemic dorsolateral portion of the striatum, in which there was severe neuronal loss. There was no significant depletion of NADPH-diaphorase-positive neurons in the striatum or cerebral cortex. Concentrations of neuropeptide Y-like and somatostatin-like immunoreactivity were unchanged despite a significant 25% depletion of substance P-like immunoreactivity and gamma-aminobutyric acid. Ischemic brain damage may be mediated by a neurotoxic effect of glutamate acting at the N-methyl-D-aspartate (NMDA) receptor. Previous studies of NMDA excitotoxin lesions in rat striatum have shown a sparing of neurons containing NADPH-diaphorase, somatostatin, and neuropeptide Y. The similar sparing of these neurons following ischemic lesions in gerbil striatum provides further evidence that NMDA receptor activation may play a role in ischemic injury.
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PMID:Selective sparing of NADPH-diaphorase-somatostatin-neuropeptide Y neurons in ischemic gerbil striatum. 197 76

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.
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PMID:Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats. 197 32

It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.
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PMID:Differences in ischemia-induced accumulation of amino acids in the cat cortex. 197 18

The mature, healthy, non-starved mammalian brain uses glucose only as a source of energy in the form of ATP, which is necessary for several metabolic processes, such as the maintenance of cellular homeostasis via ion homeostasis, maintenance of the integrity of cellular compartments, and intracellular transportation processes for the formation of several neurotransmitters, neurotransmission itself and a few anabolic reactions. Glucose breakdown contributes to the formation of the neurotransmitters: acetylcholine, glutamate, aspartate, gamma-aminobutyrate, and glycine. Normal cerebral aging is associated with an incipient perturbation in both cerebral glucose and related metabolism, that determines an energy deficit and thus an imbalance in cell homeostasis after the 7th or 8th decade of human life, indicating a threshold phenomenon. This is evidenced by morphological/morphobiological abnormalities comprising neuronal loss and structural changes. These events are thought to cause a marked reduction in the biological plasticity of the brain, which may be severely involved after additional stress situations such as ischemia, hypoxia or hypoglycemia. The age-related increasing perturbation of neuronal homeostasis may represent a stress situation capable of inducing heat shock proteins effecting gene activity. Thus, several age-related metabolic abnormalities at the cellular level, starting with a deficient neuronal glucose and energy metabolism, can be regarded as risk factors for neuronal damage and death, and hence reduced mental capacity.
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PMID:Brain glucose and energy metabolism during normal aging. 198 30

The concentrations of free and peptide-bound amino acids aspartate (Asp), glutamate (Glu), glycine (Gly) and gamma-aminobutyric acid (GABA) were studied following ischemia and recirculation in the ventral and dorsal gray matter of the rabbit spinal cord. No changes in the concentration of amino acids following ten minutes (min) of ischemia and four days of recovery were found. The most significant change after 20 min, and especially 40 min, of ischemia was a decrease in free Asp and GABA levels in both parts of the gray matter. The relatively greater decrease in the concentration of free amino acids in the ventral horns corresponds with the greater morphological damage to this part of spinal cord following ischemia. Following 40 min of ischemia and recirculation decrease in peptide-bound Glu in the ventral horns and Asp and Glu in the dorsal horns was found.
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PMID:Free and peptide-bound amino acids as indicators of ischemic damage of the rabbit spinal cord. 198 55


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