Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injection of endothelin-1 (9 pmol) into the lateral cerebral ventricle of rats produced barrel-rotations, convulsions, tonic hindlimb extensions, facial clonus, and kinetic ataxia for up to 45 min. Quantitative metabolic autoradiographs produced from the [14C]deoxyglucose method and analyzed over 60 individual brain structures or subregions revealed intense hypermetabolism in periventricular tissues close to the injection site and in many of their efferent projection sites. Histological examination of these areas proved that this dose of endothelin was without toxic or ischemic effects on neurons or glial cells. Structures metabolically affected ipsilateral to injection were caudate nucleus (+164%), lateral septal nucleus (+270%), and two white matter tracts--corpus callosum (+236%) and hippocampal fimbria (+318%). Distant stimulated structures included cerebellar cortical layers, but not cerebellar nuclei or white matter. Increased rates of glucose metabolism among many other nuclei, particularly distinct subunits of the hippocampal formation and structures in contact with the ventricular system, signify that endothelin induced widespread metabolic stimulation over much of the neuraxis. Furthermore, although the 9 pmol concentration of endothelin produced convulsive movements and diverse metabolic stimulation, it did not evoke detectable electroencephalographic seizure activity assessed by intra- or extracerebral electroencephalography. Both the convulsions and hypermetabolic activation were inhibited by intraventricular pretreatment with the dihydropyridine calcium-channel antagonist, nimodipine. The results identify endothelin-1 as a calcium-mediated 'convulsive' peptide with selective stimulatory effects on cerebral glucose metabolism.
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PMID:Cerebral hypermetabolism produced by intraventricular endothelin-1 in rats: inhibition by nimodipine. 132 10

Injection of the neuropeptide, endothelin-1 (ET, range of 3-9 pmol), into a lateral ventricle (ICV) of rats produced barrel rolling and other convulsions including ataxia, forelimb and facial clonus, nystagmus, and tonic extension of the tail and hindlimbs. Using the quantitative autoradiographic [14C]deoxyglucose method, we resolved the focal hypermetabolic correlates of the convulsive activity in numerous brain regions. The present study tested whether the effects of ET were dose dependent by assessing 13 behavioral, 9 physiological, and brain metabolic responses in six individual structures of rats treated separately with ICV ET in doses between 1.5 and 18 pmol. Barrel-rolling convulsions, having a threshold for onset at 3 pmol, displayed increased incidence and severity, and a shorter latency to onset, with the higher ET doses. Within 10-20 min, ET evoked dose-dependent increases in mean arterial pressure and plasma glucose levels, and a significant reduction in arterial PCO2. Among brain structures, the periventricular caudate nucleus near the injection site had an elevated rate of glucose metabolism (+60%) at a 3 pmol threshold. The substantia nigra pars reticulata, medial terminal nucleus of the accessory optic tract, rostral lamella of the inferior olivary nucleus, cerebellar paramedian lobule, and cerebellar copula pyramis, all of which have moderate to dense populations of ET-1 receptors and are related by anatomical connections, displayed significant metabolic stimulation by 9 pmol ET (+47 to +122%). The behavioral, physiological, and focal hypermetabolic effects of the central ET appear to be time coordinated, interrelated, and dose dependent. Identification of the threshold dose for central actions of ET at 3 pmol ICV reveals this peptide as the most potent neuroactive substance yet described in vivo.
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PMID:Dose-related potent brain stimulation by the neuropeptide endothelin-1 after intraventricular administration in conscious rats. 761 31

The effects of an endothelin ET(A)-receptor selective antagonist, S-0139, were examined using dogs given endothelin-1 (ET-1) into the subarachnoid space. ET-1 at 40 pmol apparently constricted the basilar artery in anesthetized dogs and caused various grades of ataxia, facial clonus, nystagmus and other features in conscious dogs, partially mimicking those which have been reported for conscious rats. S-0139 could completely inhibit both the vasoconstriction and behavioral changes. It could also alleviate the behavioral changes caused by ET-1 in conscious dogs when given after the severe ataxia. We concluded that ET-1 in the subarachnoid space produces behavioral changes via endothelin ET(A)-receptor mediation similar to its cerebral vasoconstricting action, at least, in dogs.
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PMID:Effects of an endothelin ET(A)-receptor antagonist, S-0139, on cerebral vasospasm and behavioral changes in dogs intracisternally administered endothelin-1. 951 5