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

Dopamine (DA), serotonin (5-HT), tryptophan (TRP), 5-hydroxyindole acetic acid (5-HIAA), and GABA were assayed spectrofluorometrically in various regions of 16 human post-mortem brains with acute and old cerebral infarction. In both recent and older strokes a total depletion of DA and 5-HT in the necrotic tissue was associated with mild reduction of these compounds in remote non-ischemic areas of the injured, and less of the contralateral cerebral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed considerable accumulation of both 5-HT and 5-HIAA. Marked elevation of the 5-HT precursor TRP and of GABA was present in both the necrotic center and perifocal edema of acute infarcts, which also showed a mild reduction of total proteins. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA with normal TRP levels, indicating normalization of the previously increased 5-HT metabolism and turnover after decrease of acute cerebral edema. These data which confirm previous studies in experimental cerebral ischemia and stroke indicate that disorders in the metabolism of brain monoamines and other putative neurotransmitters contribute to the development of postischemic brain damage and the complicating cerebral edema. They are also in keeping with the concept that unilateral focal ischemia produces bilateral effects on brain monoamines.
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PMID:Changes of some putative neurotransmitters in human cerebral infarction. 3 76

In gerbil brain, levels of hydroxyl radicals (OH.) and neurotransmitters such as glutamate, aspartate, GABA (gamma aminobutyric acid) are low at birth, reach a plateau and decrease with age. On the other hand, when gerbils are exposed to an ischemia reperfusion insult (IRI) the older animals have a higher stroke index and hydroxyl radical as well as glutamate and other neuromediators are concomitantly increased. This discrepancy is probably due to differences in the ability of old individuals to respond to oxidative stress. The still incompletely understood relationship between oxidative damage to proteins and accumulation of amino acids, which have an important role as neurotransmitters at physiologic concentrations, but may become neurotoxic at high concentrations, is discussed.
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PMID:Free radicals and neurotransmitters in gerbil brain. Influence of age and ischemia reperfusion insult. 136 Feb 81

Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.
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PMID:Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA. 136 7

The mongolian gerbil was introduced as a stroke model because of its incomplete circle of Willis. Unilateral carotid ligation ischemia produced in such a fashion was not effective in all gerbils. We have selected gerbils by examination of the ocular fundus to study the level of amino acids and hydroxyl free radicals (OH0 formation of DHBA, dihydroxybenzoic acid, from salicylate) in gerbil cerebral ischemia. Only gerbils with absence of retinal blood after ligation were selected as sensitive. One group (sham operated) served as control. The other group was subjected to unilateral left carotid occlusion with a clip during 30 minutes and classified as sensitive and non sensitive. Sixty minutes after release of the clip, levels of aspartate, glutamate, GABA were quantified in left hippocampus and in left retina. Levels of 2,5 DHBA (2,5 dihydroxybenzoic acid) were quantified in left retina and in left hemisphere. Compared to sham operated group, levels of aspartate (greater than 371%), glutamate (greater than 318%), GABA (greater than 122%) and 2,5 DHBA (greater than 385%) significantly increased in the group subjected to carotid occlusion. The determination of concentrations of amino acids and 2,5 DHBA in sensitive gerbils was a suitable method to study cerebral and retinal ischemia.
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PMID:Accumulation of amino acids and hydroxyl free radicals in brain and retina of gerbil after transient ischemia. 191 70

The levels of the neurotransmitter amino acids glutamate, aspartate, and GABA were determined in different brain regions during ischemia and post-ischemic recirculation periods using the unilateral carotid artery occlusion model of stroke in gerbils. The levels of glutamate, aspartate and GABA in ischemic hemisphere were increased significantly by 10 min of ischemia and later declined with time. Reperfusion for 30 min following 10 min. of ischemia further enhanced the levels of glutamate and aspartate. Increase in GABA levels were found during early periods of reperfusion. Regional variations in the changes of amino acids' levels were noticed following ischemia. Hippocampus showed the highest increase in glutamate levels followed by striatum and cerebral cortex. Aspartate levels in striatum and hippocampus increased during 10 min ischemia (46% and 30%) and recirculation (70% and 79%), whereas in cerebral cortex the levels were doubled only during recirculation. Ischemia induced elevations of GABA levels were observed in cerebral cortex (68%) and in hippocampus (30%), and the levels were normalized during recirculation. No changes in GABA levels were found in striatum. It is suggested that the large increase in the levels of excitatory neurotransmitter amino acids in brain regions specially in hippocampus during ischemia and recirculation may be one of the causal factors for ischemic brain damage.
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PMID:Changes in regional levels of putative neurotransmitter amino acids in brain under unilateral forebrain ischemia. 257 Oct 93

Selective degeneration of pyramidal neurons in regions CA1 and CA3 of the hippocampus is a common structural correlate of several neurodegenerative conditions including Alzheimer's disease, epilepsy and stroke. Several lines of evidence suggest that glutamate, an excitatory neurotransmitter intimately involved in learning and memory processes, may also be involved in hippocampal neurodegeneration. High levels of glutamate are toxic to select groups of pyramidal neurons both in vivo and in vitro and subtoxic levels of glutamate can cause the regression of pyramidal neuron dendrites. In order to determine the basis for this selective vulnerability we employed two rat hippocampal culture paradigms. The first paradigm consisted of neurons isolated from different hippocampal regions (CA1, CA2, CA3, dentate gyrus). Selective vulnerability in the isolated neurons mirrored the selective cell loss that occurs in situ. Dentate granule cells and CA2 pyramidal-like neurons were relatively resistant to glutamate-induced neurodegeneration, while CA1 and CA3 pyramidal neurons were significantly more vulnerable. The second paradigm consisted of sister pyramidal neurons arising from a common progenitor cell. Sister neurons were found to be either both sensitive or both resistant to the degenerative effects of glutamate indicating that mitotic history was an important determinant of selective vulnerability. Experiments which examined the cellular mechanisms underlying selective vulnerability revealed that glutamate caused a large and sustained rise in intracellular calcium levels only in vulnerable neurons. Pharmacological experiments with glutamate receptor antagonists, the inhibitory transmitter GABA, and calcium blockers indicated that vulnerable, but not resistant, neurons expressed glutamate receptors which mediated large rises in intracellular calcium and subsequent degeneration. These results indicate that intrinsic differences in the expression of glutamate receptors linked to calcium influx may account for selective neuronal vulnerability. Treatments which block glutamate receptors, suppress electrical activity, or block calcium channels directly may prove useful in preventing the degeneration of the hippocampal circuitry whose integrity is critical for learning and memory processes.
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PMID:Intrinsic factors in the selective vulnerability of hippocampal pyramidal neurons. 269 Jan 6

This article surveys the conventional neurotransmitters and modulatory neuropeptides that are found in the cerebral cortex and attempts to place them into the perspective of both intracortical circuitry and cortical disease. The distribution of these substances is related, where possible, to particular types of cortical neuron or to afferent or efferent fibers. Their physiological actions, where known, on cortical neurons are surveyed, and their potential roles in disease states such as the dementias, epilepsy, and stroke are assessed. Conventional transmitters that occur in afferent fibers to the cortex from brain-stem and basal forebrain sites are: serotonin, noradrenaline, dopamine, and acetylcholine. All of these except dopamine are distributed to all cortical areas: dopamine is distributed to frontal and cingulate areas only. The transmitter in thalamic afferent systems is unknown. Gamma aminobutyric acid (GABA) is the transmitter used by the majority of cortical interneurons and has a profound effect upon the shaping of receptive field properties. The vast majority of the known cortical peptides are found in GABAergic neurons, and the possibility exists that they may act as trophic substances for other neurons. Levels of certain neuropeptides decline in cases of dementia of cortical origin. Acetylcholine is the only other known transmitter of cortical neurons. It, too, is contained in neurons that also contain a neuropeptide. The transmitter(s) used by excitatory cortical interneurons and by the efferent pyramidal cells is unknown, but it may be glutamate or aspartate. It is possible that excitotoxins released in anoxic disease of the cortex may produce damage by acting on receptors for these or related transmitter agents.
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PMID:Neurotransmitters in the cerebral cortex. 287 11

Evidence supporting the hypothesis that GABA-ergic mechanisms are involved in controlling mammalian cardiovascular function has been reviewed and analyzed. In vivo and in vitro studies with GABA-agonists and GABA-antagonists have revealed that activation of GABA-receptors is involved in the control of blood pressure and heart rate. Further studies conducted with agents that modify central and/or peripheral GABA-ergic systems could lead to the discovery of drugs that might be useful for treating certain cardiovascular disorders in man, such as hypertension and stroke, and should increase our understanding of the pathophysiological bases of such disorders.
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PMID:gamma-Aminobutyric acid and cardiovascular function. 630 35

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis. 631 38

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with pre-ischemic levels and by a histological assessment of the extent of neuronal degeneration of the CA1 area of the hippocampus. 3. The GABA transport inhibitor CI-966 (10 mg/kg i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CI-966 reduced the extent of stroke injury as assessed by locomotor activity and measurement of hippocampal CA1 pyramidal cell injury. 4. It is proposed that enhancement of extracellular GABA levels during ischemia accounts for the cerebroprotective actions of CI-966.
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PMID:CI-966, a GABA uptake inhibitor, antagonizes ischemia-induced neuronal degeneration in the gerbil. 755 51


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