Elevated blood purine levels as a biomarker of seizures and epilepsy

Objective: There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to- use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activit...

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Autores: Beamer, Edward, Lacey, Austin, Alves, Mariana, Conte, Giorgia, Tian, Faming, De Diego García, Laura, Khalil, Mohamed, Rosenow, Felix, Delanty, Norman, Dale, Nicholas, El-Naggar, Hany, Henshall, DC, Engel, Tobias
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/132595
Acceso en línea:https://hdl.handle.net/20.500.14352/132595
Access Level:acceso abierto
Palabra clave:616.853
616-074:543.645
Diagnosis
Point-of-care device
Purines
Seizures
Epilepsy
Biología molecular (Biología)
Bioquímica (Medicina)
Neurociencias (Medicina)
2403 Bioquímica
2302.21 Biología Molecular
2490 Neurociencias
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spelling Elevated blood purine levels as a biomarker of seizures and epilepsyBeamer, EdwardLacey, AustinAlves, MarianaConte, GiorgiaTian, FamingDe Diego García, LauraKhalil, MohamedRosenow, FelixDelanty, NormanDale, NicholasEl-Naggar, HanyHenshall, DCEngel, Tobias616.853616-074:543.645DiagnosisPoint-of-care devicePurinesSeizuresEpilepsyBiología molecular (Biología)Bioquímica (Medicina)Neurociencias (Medicina)2403 Bioquímica2302.21 Biología Molecular2490 NeurocienciasObjective: There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to- use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy. Methods: Blood purine concentrations were measured via a point-of-care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra-amygdala kainic acid-induced status epilepticus and in video-electroencephalogram (EEG)-monitored adult patients with epilepsy. Results: In mice, blood purine concentrations were rapidly increased approximately two-to threefold after status epilepticus (2.32 ± .40 μmol·L–1 [control] vs. 8.93 ± 1.03 μmol·L–1 [after status epilepticus]), and levels correlated with seizure burden and postseizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video-EEG-diagnosed epilepsy (2.39 ± .34 μmol·L–1 [control, n = 13] s. 4.35 ± .38 μmol·L–1 [epilepsy, n = 26]). Significance: Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low-volume bedside test to support the diagnosis of seizures and epilepsy.John Wiley & Sons, IncUniversidad Complutense de Madrid20212021-05-2020212021-05-20journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/132595reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengHRB HRA-POR-2015-1243 Not availableSFI 17 CDASFI 18 TIDASFI 13 SIRGERDF 16 RC EUopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1325952026-06-02T12:44:21Z
dc.title.none.fl_str_mv Elevated blood purine levels as a biomarker of seizures and epilepsy
title Elevated blood purine levels as a biomarker of seizures and epilepsy
spellingShingle Elevated blood purine levels as a biomarker of seizures and epilepsy
Beamer, Edward
616.853
616-074:543.645
Diagnosis
Point-of-care device
Purines
Seizures
Epilepsy
Biología molecular (Biología)
Bioquímica (Medicina)
Neurociencias (Medicina)
2403 Bioquímica
2302.21 Biología Molecular
2490 Neurociencias
title_short Elevated blood purine levels as a biomarker of seizures and epilepsy
title_full Elevated blood purine levels as a biomarker of seizures and epilepsy
title_fullStr Elevated blood purine levels as a biomarker of seizures and epilepsy
title_full_unstemmed Elevated blood purine levels as a biomarker of seizures and epilepsy
title_sort Elevated blood purine levels as a biomarker of seizures and epilepsy
dc.creator.none.fl_str_mv Beamer, Edward
Lacey, Austin
Alves, Mariana
Conte, Giorgia
Tian, Faming
De Diego García, Laura
Khalil, Mohamed
Rosenow, Felix
Delanty, Norman
Dale, Nicholas
El-Naggar, Hany
Henshall, DC
Engel, Tobias
author Beamer, Edward
author_facet Beamer, Edward
Lacey, Austin
Alves, Mariana
Conte, Giorgia
Tian, Faming
De Diego García, Laura
Khalil, Mohamed
Rosenow, Felix
Delanty, Norman
Dale, Nicholas
El-Naggar, Hany
Henshall, DC
Engel, Tobias
author_role author
author2 Lacey, Austin
Alves, Mariana
Conte, Giorgia
Tian, Faming
De Diego García, Laura
Khalil, Mohamed
Rosenow, Felix
Delanty, Norman
Dale, Nicholas
El-Naggar, Hany
Henshall, DC
Engel, Tobias
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616.853
616-074:543.645
Diagnosis
Point-of-care device
Purines
Seizures
Epilepsy
Biología molecular (Biología)
Bioquímica (Medicina)
Neurociencias (Medicina)
2403 Bioquímica
2302.21 Biología Molecular
2490 Neurociencias
topic 616.853
616-074:543.645
Diagnosis
Point-of-care device
Purines
Seizures
Epilepsy
Biología molecular (Biología)
Bioquímica (Medicina)
Neurociencias (Medicina)
2403 Bioquímica
2302.21 Biología Molecular
2490 Neurociencias
description Objective: There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to- use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy. Methods: Blood purine concentrations were measured via a point-of-care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra-amygdala kainic acid-induced status epilepticus and in video-electroencephalogram (EEG)-monitored adult patients with epilepsy. Results: In mice, blood purine concentrations were rapidly increased approximately two-to threefold after status epilepticus (2.32 ± .40 μmol·L–1 [control] vs. 8.93 ± 1.03 μmol·L–1 [after status epilepticus]), and levels correlated with seizure burden and postseizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video-EEG-diagnosed epilepsy (2.39 ± .34 μmol·L–1 [control, n = 13] s. 4.35 ± .38 μmol·L–1 [epilepsy, n = 26]). Significance: Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low-volume bedside test to support the diagnosis of seizures and epilepsy.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-05-20
2021
2021-05-20
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/132595
url https://hdl.handle.net/20.500.14352/132595
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv HRB HRA-POR-2015-1243 Not available
SFI 17 CDA
SFI 18 TIDA
SFI 13 SIRG
ERDF 16 RC EU
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons, Inc
publisher.none.fl_str_mv John Wiley & Sons, Inc
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155