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Article: High concentrations of extracellular potassium enhance bacterial endotoxin lipopolysaccharide-induced neurotoxicity in glia-neuron mixed cultures

TitleHigh concentrations of extracellular potassium enhance bacterial endotoxin lipopolysaccharide-induced neurotoxicity in glia-neuron mixed cultures
Authors
Issue Date2000
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience
Citation
Neuroscience, 2000, v. 97 n. 4, p. 757-764 How to Cite?
AbstractA sudden increase in extracellular potassium ions (K+) often occurs in cerebral ischemia and after brain trauma. This increase of extracellular K+ constitutes the basis for spreading depression across the cerebral cortex, resulting in the expansion of neuronal death after ischemic and traumatic brain injuries. Besides spreading depression, it has become clear that cerebral inflammation also is a key factor contributing to secondary brain injury in acute neurological disorders. Experiments to validate the relationship between elevated levels of extracellular K+ and inflammation have not been studied. This study aims to elucidate the roles of high concentrations of extracellular K+ in bacterial endotoxin lipopolysaccharide-induced production of inflammatory factors. Increased concentration of KCl in the medium (20 mM) significantly enhanced neurotoxicity by lipopolysaccharide in glia-neuron mixed cultures. To delineate the underlying mechanisms of increased neurotoxicity, the effects of high extracellular K+ were examined by using mixed glial cultures. KCl at 20 mM significantly enhanced nitrite, an index for nitric oxide, production by about twofold, and was pronounced from 24 to 48 h, depending on the concentration of KCl. Besides nitric oxide production of tumor necrosis factor-α was also enhanced. The augmentative effects of high KCl on the production of inflammatory factors were probably due to the further activation of microglia, since high KCl also enhanced the production of tumor necrosis factor-α in microglia-enriched cultures. The increased production of nitrite by high K+ was eliminated through use of a K+-blocker. Taken together, the results show that increases of extracellular K+ concentrations in spreading depression augment lipopolysaccharide-elicited neurotoxicity, because production of inflammatory factors such as nitric oxide and tumor necrosis factor-α are potentiated. Since spreading depression and cerebral inflammation are important in acute neurological disorders, the present results suggest a biochemical mechanism: elevated extracellular K+ concentrations augment glial inflammatory responses, and thus the neurotoxicity.
Persistent Identifierhttp://hdl.handle.net/10722/149592
ISSN
2015 Impact Factor: 3.231
2015 SCImago Journal Rankings: 1.768
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChang, RCCen_US
dc.contributor.authorHudson, PMen_US
dc.contributor.authorWilson, BCen_US
dc.contributor.authorLiu, Ben_US
dc.contributor.authorAbel, Hen_US
dc.contributor.authorHong, JSen_US
dc.date.accessioned2012-06-26T05:55:41Z-
dc.date.available2012-06-26T05:55:41Z-
dc.date.issued2000en_US
dc.identifier.citationNeuroscience, 2000, v. 97 n. 4, p. 757-764en_US
dc.identifier.issn0306-4522en_US
dc.identifier.urihttp://hdl.handle.net/10722/149592-
dc.description.abstractA sudden increase in extracellular potassium ions (K+) often occurs in cerebral ischemia and after brain trauma. This increase of extracellular K+ constitutes the basis for spreading depression across the cerebral cortex, resulting in the expansion of neuronal death after ischemic and traumatic brain injuries. Besides spreading depression, it has become clear that cerebral inflammation also is a key factor contributing to secondary brain injury in acute neurological disorders. Experiments to validate the relationship between elevated levels of extracellular K+ and inflammation have not been studied. This study aims to elucidate the roles of high concentrations of extracellular K+ in bacterial endotoxin lipopolysaccharide-induced production of inflammatory factors. Increased concentration of KCl in the medium (20 mM) significantly enhanced neurotoxicity by lipopolysaccharide in glia-neuron mixed cultures. To delineate the underlying mechanisms of increased neurotoxicity, the effects of high extracellular K+ were examined by using mixed glial cultures. KCl at 20 mM significantly enhanced nitrite, an index for nitric oxide, production by about twofold, and was pronounced from 24 to 48 h, depending on the concentration of KCl. Besides nitric oxide production of tumor necrosis factor-α was also enhanced. The augmentative effects of high KCl on the production of inflammatory factors were probably due to the further activation of microglia, since high KCl also enhanced the production of tumor necrosis factor-α in microglia-enriched cultures. The increased production of nitrite by high K+ was eliminated through use of a K+-blocker. Taken together, the results show that increases of extracellular K+ concentrations in spreading depression augment lipopolysaccharide-elicited neurotoxicity, because production of inflammatory factors such as nitric oxide and tumor necrosis factor-α are potentiated. Since spreading depression and cerebral inflammation are important in acute neurological disorders, the present results suggest a biochemical mechanism: elevated extracellular K+ concentrations augment glial inflammatory responses, and thus the neurotoxicity.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscienceen_US
dc.relation.ispartofNeuroscienceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Nucleus - Ultrastructureen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCerebral Cortex - Cytology - Physiologyen_US
dc.subject.meshCharybdotoxin - Pharmacologyen_US
dc.subject.meshCoculture Techniquesen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshEmbryo, Mammalianen_US
dc.subject.meshExtracellular Space - Physiologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshLipopolysaccharides - Toxicityen_US
dc.subject.meshMiceen_US
dc.subject.meshNeuroglia - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshNeurons - Cytology - Drug Effects - Physiologyen_US
dc.subject.meshNeurotoxins - Toxicityen_US
dc.subject.meshNitrites - Metabolismen_US
dc.subject.meshPotassium Chloride - Pharmacologyen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Analysisen_US
dc.titleHigh concentrations of extracellular potassium enhance bacterial endotoxin lipopolysaccharide-induced neurotoxicity in glia-neuron mixed culturesen_US
dc.typeArticleen_US
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_US
dc.identifier.authorityChang, RCC=rp00470en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0306-4522(00)00059-2en_US
dc.identifier.pmid10842021-
dc.identifier.scopuseid_2-s2.0-0034090501en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034090501&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume97en_US
dc.identifier.issue4en_US
dc.identifier.spage757en_US
dc.identifier.epage764en_US
dc.identifier.isiWOS:000087641700016-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridChang, RCC=7403713410en_US
dc.identifier.scopusauthoridHudson, PM=35566903000en_US
dc.identifier.scopusauthoridWilson, BC=35243580200en_US
dc.identifier.scopusauthoridLiu, B=36079151900en_US
dc.identifier.scopusauthoridAbel, H=7103073193en_US
dc.identifier.scopusauthoridHong, JS=34770185100en_US

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