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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A derivate of gamma-aminobutyric acid was found to have a favourable therapeutic effect in patients with forced weeping (weeping sickness). All 10 treated cases were shown to have motor neuron lesions resulting from other cerebral changer (cerebrovascular accident, brain atrophy, diffuse vascular changes).
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PMID:[Treatment of forced weeping (author's transl)]. 101 9

The N-methyl-D-aspartate (NMDA) receptor is believed to play a major role in learning and in excitotoxic neuronal damage associated with stroke and epilepsy. Pregnenolone sulfate, a neurosteroid, specifically enhances NMDA-gated currents in spinal cord neurons, while inhibiting receptors for the inhibitory amino acids glycine and gamma-aminobutyric acid, as well as non-NMDA glutamate receptors. This observation is consistent with the hypothesis that neurosteroids such as pregnenolone sulfate are involved in regulating the balance between excitation and inhibition in the central nervous system.
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PMID:Pregnenolone sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor. 165 10

We examined the role of the locus coeruleus (LC) in the regulation of the hemodynamics and sympathetic nerve activity in anesthetized rats. Unilateral microinjection into the LC of the excitatory amino acid, L-glutamate (Glu), elicited dose-dependent decreases in arterial pressure (AP) and heart rate (HR). The bradycardic response was partially attenuated after intravenous injection of atropine sulfate, but the greater part of this response still remained. Interruption of the ascending projections of the LC by midbrain transection did not affect the depressor and bradycardic responses elicited by chemical stimulation. The renal sympathetic nerve activity showed transient but strong inhibition with this stimulation. Cardiac output was measured using an electromagnetic flowmeter implanted in the ascending aorta. The stroke volume and total peripheral resistance (TPR) were calculated. Microinjection of Glu elicited a significant decrease in TPR and slight decreases in cardiac output and stroke volume. Microinjection of the inhibitory amino acid, gamma-aminobutyric acid (GABA), or the alpha 2-adrenergic agonist, clonidine, exerted no effect on AP and HR. The present results therefore suggest that: (1) the LC neurons have an inhibitory influence on the sympathetic nervous system, and stimulation of these neurons can elicit depressor and bradycardic responses; (2) the depressor response was produced predominantly as a result of a decrease in vascular resistance, rather than a decrease in cardiac output; (3) these inhibitory responses may be provided not via the ascending projections of the LC; and (4) the LC neurons do not have a tonic influence on the cardiovascular system.
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PMID:Chemical stimulation of the locus coeruleus: inhibitory effects on hemodynamics and renal sympathetic nerve activity. 168 67

1. The effect of chlormethiazole, and other drugs which potentiate gamma-aminobutyric acid (GABA) function on delayed neuronal death in the hippocampus has been examined in the gerbil. 2. Chlormethiazole (100 mg kg-1, i.p.) and two other drugs previously reported to be neuroprotective (dizocilpine, 3 mg kg-1, i.p. and ifenprodil, 4 mg kg-1, i.p.) were all found to prevent neurodegeneration of CA1/CA2 neurones in the hippocampus when given 30 min before a 5 min episode of bilateral carotid artery occlusion. 3. Chlormethiazole (100 mg kg-1) was neuroprotective when given up to 3 h, after the ischaemic episode. 4. Given 1 h after the cartoid artery occlusion, chlormethiazole produced significant protection against hippocampal neurodegeneration at a dose of 50 mg kg-1, but not at 25 mg kg-1. 5. Phenobarbitone (100 mg kg-1, i.p.) and Saffan (alphaxalone, 45 mg kg-1 plus alphadalone, 15 mg kg-1, i.p.) were not protective when given 1 h after the ischaemic episode while pentobarbitone (30 mg kg-1, i.p.) had a modest protective effect. 6. Evidence is presented to show that neither the operating procedure nor the chlormethiazole administration lowered rectal or cerebral temperature. 7. The data suggest that chlormethiazole may be a useful treatment in the prevention of neurodegeneration following stroke or cardiac arrest.
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PMID:Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. 179 7

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, including phencyclidine (PCP) and ketamine, protect against brain damage in neurological disorders such as stroke. However, these agents have psychotomimetic properties in humans and morphologically damage neurons in the cerebral cortex of rats. It is now shown that the morphological damage can be prevented by certain anticholinergic drugs or by diazepam and barbiturates, which act at the gamma-aminobutyric acid (GABA) receptor-channel complex and are known to suppress the psychotomimetic symptoms caused by ketamine. Thus, it may be possible to prevent the unwanted side effects of NMDA antagonists, thereby enhancing their utility as neuroprotective drugs.
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PMID:NMDA antagonist neurotoxicity: mechanism and prevention. 183 99

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.
Stroke 1990 Oct
PMID:Differences in ischemia-induced accumulation of amino acids in the cat cortex. 197 18

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.
Stroke 1990 Dec
PMID:Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil. 214 36

Recent morphologic and behavioral studies of the effects of gamma-aminobutyric acid agents on transsynaptic degeneration after cortical and striatal damage are reviewed and discussed. Following unilateral lesions of the anteromedial cortex, mild atrophy appears in the ipsilateral striatum and substantia nigra pars reticulata. Long-term diazepam administration greatly enhances this degeneration, extends the degeneration into the thalamus, and severely disrupts recovery from somatosensory asymmetries. Following unilateral excitotoxic lesions of the striatum, progressive degeneration of neurons occurs in the substantia nigra pars reticulata and efferent targets in the thalamus. This degeneration can be prevented by chronic infusion of muscimol, a gamma-aminobutyric acid agonist. Unexpectedly, this treatment did not facilitate recovery from somatosensory asymmetries. Recovery in muscimol-treated animals was impaired relative to saline-treated controls. Thus, gamma-aminobutyric acid agonists either may enhance or prevent neural atrophy secondary to brain damage, but the behavioral outcome appears to depend importantly on the excitatory and inhibitory characteristics of the affected networks.
Stroke 1990 Nov
PMID:Multilevel transneuronal degeneration after brain damage. Behavioral events and effects of anticonvulsant gamma-aminobutyric acid-related drugs. 223 72

Previous studies have shown that pyramidal neurons in hippocampal regions CA1 and CA3 are selectively vulnerable in several neurodegenerative disorders and that a subpopulation of pyramidal neurons in cell cultures of embryonic hippocampus are sensitive to glutamate neurotoxicity. In order to determine whether the patterns of cell loss seen in situ correlate with intrinsic differences in neuronal sensitivities to glutamate-induced degeneration acquired during development, we characterized cultures established from different regions of postnatal rat hippocampus and then examined neuronal sensitivity to glutamate. Tissue corresponding to the dentate gyrus (DG) and regions CA1, CA2 and CA3 of Ammon's horn was removed by microdissection from transverse hippocampal slices and was used to establish cultures of dissociated cells. Cultures from all 4 regions contained 3 major morphological classes of neurons; pyramidal-like, bipolar and stellate. Pyramidal-like neurons comprised the majority of neurons in all cultures; these neurons extended one long and branching axon, and one or more short dendrites. Immunocytochemistry showed that all neurons possessed high levels of glutamate-like and gamma-aminobutyric acid (GABA)-like immunoreactivity when grown in isolation. In contrast, when bipolar and pyramidal neurons were cultured in contact with glial cells, glutamate and GABA immunoreactivity were selectively reduced in the bipolar and pyramidal cells, respectively, suggesting that cell interactions influence neurotransmitter phenotype. Subpopulations of hippocampal neurons from each hippocampal region were vulnerable to glutamate-induced neurotoxicity. Bipolar and stellate cells were resistant to glutamate, while pyramidal-like neurons showed varying degrees of sensitivity to glutamate depending upon which region they were taken from. Experiments with specific glutamate receptor agonists and antagonists demonstrated that both non N-methyl-D-aspartic acid (NMDA) receptors and NMDA receptors mediated glutamate-induced degeneration. There were clear differences in the vulnerability of the pyramidal-like neuron populations in cultures from the different hippocampal regions. The rank order of the vulnerability of pyramidal-like neurons to glutamate-induced neurodegeneration between regions in culture was: DG less than CA2 less than CA3 less than CA1. This pattern of selective vulnerability in cell culture corresponds directly to the pattern of selective cell loss seen in situ in Alzheimer's disease, epilepsy, and stroke suggesting that intrinsic neuronal differences in glutamate sensitivity may be involved in these disorders.
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PMID:Development and selective neurodegeneration in cell cultures from different hippocampal regions. 256 50

Proton nuclear magnetic resonance (NMR) spectroscopy of perchloric acid tissue extracts has been used to follow serial postischemic changes in the levels of metabolites in the hippocampus, cerebellum, frontal lobes, and parietal/occipital lobes in a rat model of short-duration (10 minutes) forebrain ischemia. Shortly (10 minutes, 1 hour) after the ischemic insult, the levels of the amino acids alanine and gamma-aminobutyric acid are elevated and that of glutamate is depressed in all regions except the cerebellum. The levels of these species return to control values by 24 hours postischemia. No changes are observed in the levels of aspartate or N-acetylaspartate. Greatly elevated levels of acetate 10 minutes postischemia, particularly in the hippocampus, may be due in part to metabolic degradation of fatty acids released due to membrane breakdown. Elevated levels of lactate persist for up to 7 days postischemia, suggesting that normal mitochondrial functioning is not fully restored following the ischemic insult.
Stroke 1989 May
PMID:Nuclear magnetic resonance study of regional metabolism after forebrain ischemia in rats. 271 4


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