High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier

Autores
Ceaglio, Natalia Analia; Orozco, Gustavo; Etcheverrigaray, Marina; Mattio, Mónica Cristina; Kratje, Ricardo Bertoldo; Perotti, Norma Maria; Oggero Eberhardt, Marcos Rafael
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
An important issue to be considered when studying a new drug for treatment of central nervous system (CNS) diseases is its ability to cross the blood–brain barrier (BBB) and distribute throughout the brain. As cerebrospinal fluid (CSF) has demonstrated to be an invaluable reservoir to study CNS availability of therapeutic proteins, we have developed an improved method for CSF sampling from the cisterna magna of rats. The technique enables the simple and rapid collection of adequate quantities (50–75 μl) of blood-free CSF, rendering a high percentage of animal survival (99%) without clinic or neurological consequences. Its success in avoiding blood contamination of CSF lays in the use of a mixture of lidocaine/ephinephrine topically injected in the rat's suboccipital area and neck. Another relevant feature of the methodology is its low cost, since the puncture device can be easily assembled with cheap and available materials and, more importantly, neither expensive stereotaxic equipment nor frame is required. The present method is demonstrated by studying the CSF pharmacokinetics of recombinant human erythropoietin (rhEPO), a well-studied therapeutic candidate for neurological diseases. Moreover, we applied this technique to evaluate a strategy of osmotic disruption of the BBB to achieve a faster delivery of rhEPO into the CNS.
Fil: Ceaglio, Natalia Analia. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Orozco, Gustavo. Zelltek S.A.; Argentina
Fil: Etcheverrigaray, Marina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina
Fil: Mattio, Mónica Cristina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Kratje, Ricardo Bertoldo. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Perotti, Norma Maria. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Materia
Cerebrospinal Fluid
Blood-Brain Barrier
Sampling Method
Osmotic Disruption
Rhepo
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6392
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrierCeaglio, Natalia AnaliaOrozco, GustavoEtcheverrigaray, MarinaMattio, Mónica CristinaKratje, Ricardo BertoldoPerotti, Norma MariaOggero Eberhardt, Marcos RafaelCerebrospinal FluidBlood-Brain BarrierSampling MethodOsmotic DisruptionRhepohttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3An important issue to be considered when studying a new drug for treatment of central nervous system (CNS) diseases is its ability to cross the blood–brain barrier (BBB) and distribute throughout the brain. As cerebrospinal fluid (CSF) has demonstrated to be an invaluable reservoir to study CNS availability of therapeutic proteins, we have developed an improved method for CSF sampling from the cisterna magna of rats. The technique enables the simple and rapid collection of adequate quantities (50–75 μl) of blood-free CSF, rendering a high percentage of animal survival (99%) without clinic or neurological consequences. Its success in avoiding blood contamination of CSF lays in the use of a mixture of lidocaine/ephinephrine topically injected in the rat's suboccipital area and neck. Another relevant feature of the methodology is its low cost, since the puncture device can be easily assembled with cheap and available materials and, more importantly, neither expensive stereotaxic equipment nor frame is required. The present method is demonstrated by studying the CSF pharmacokinetics of recombinant human erythropoietin (rhEPO), a well-studied therapeutic candidate for neurological diseases. Moreover, we applied this technique to evaluate a strategy of osmotic disruption of the BBB to achieve a faster delivery of rhEPO into the CNS.Fil: Ceaglio, Natalia Analia. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; ArgentinaFil: Orozco, Gustavo. Zelltek S.A.; ArgentinaFil: Etcheverrigaray, Marina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; ArgentinaFil: Mattio, Mónica Cristina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; ArgentinaFil: Kratje, Ricardo Bertoldo. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; ArgentinaFil: Perotti, Norma Maria. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; ArgentinaFil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; ArgentinaElsevier2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6392Ceaglio, Natalia Analia; Orozco, Gustavo; Etcheverrigaray, Marina; Mattio, Mónica Cristina; Kratje, Ricardo Bertoldo; et al.; High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier; Elsevier; Journal of Neuroscience Methods; 219; 1; 9-2013; 70-750165-0270enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0165027013002471info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jneumeth.2013.07.009info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-01-08T12:49:41Zoai:ri.conicet.gov.ar:11336/6392instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-01-08 12:49:42.28CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
title High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
spellingShingle High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
Ceaglio, Natalia Analia
Cerebrospinal Fluid
Blood-Brain Barrier
Sampling Method
Osmotic Disruption
Rhepo
title_short High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
title_full High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
title_fullStr High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
title_full_unstemmed High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
title_sort High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier
dc.creator.none.fl_str_mv Ceaglio, Natalia Analia
Orozco, Gustavo
Etcheverrigaray, Marina
Mattio, Mónica Cristina
Kratje, Ricardo Bertoldo
Perotti, Norma Maria
Oggero Eberhardt, Marcos Rafael
author Ceaglio, Natalia Analia
author_facet Ceaglio, Natalia Analia
Orozco, Gustavo
Etcheverrigaray, Marina
Mattio, Mónica Cristina
Kratje, Ricardo Bertoldo
Perotti, Norma Maria
Oggero Eberhardt, Marcos Rafael
author_role author
author2 Orozco, Gustavo
Etcheverrigaray, Marina
Mattio, Mónica Cristina
Kratje, Ricardo Bertoldo
Perotti, Norma Maria
Oggero Eberhardt, Marcos Rafael
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebrospinal Fluid
Blood-Brain Barrier
Sampling Method
Osmotic Disruption
Rhepo
topic Cerebrospinal Fluid
Blood-Brain Barrier
Sampling Method
Osmotic Disruption
Rhepo
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv An important issue to be considered when studying a new drug for treatment of central nervous system (CNS) diseases is its ability to cross the blood–brain barrier (BBB) and distribute throughout the brain. As cerebrospinal fluid (CSF) has demonstrated to be an invaluable reservoir to study CNS availability of therapeutic proteins, we have developed an improved method for CSF sampling from the cisterna magna of rats. The technique enables the simple and rapid collection of adequate quantities (50–75 μl) of blood-free CSF, rendering a high percentage of animal survival (99%) without clinic or neurological consequences. Its success in avoiding blood contamination of CSF lays in the use of a mixture of lidocaine/ephinephrine topically injected in the rat's suboccipital area and neck. Another relevant feature of the methodology is its low cost, since the puncture device can be easily assembled with cheap and available materials and, more importantly, neither expensive stereotaxic equipment nor frame is required. The present method is demonstrated by studying the CSF pharmacokinetics of recombinant human erythropoietin (rhEPO), a well-studied therapeutic candidate for neurological diseases. Moreover, we applied this technique to evaluate a strategy of osmotic disruption of the BBB to achieve a faster delivery of rhEPO into the CNS.
Fil: Ceaglio, Natalia Analia. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Orozco, Gustavo. Zelltek S.A.; Argentina
Fil: Etcheverrigaray, Marina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina
Fil: Mattio, Mónica Cristina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Kratje, Ricardo Bertoldo. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
Fil: Perotti, Norma Maria. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; Argentina
Fil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Cultivos Celulares; Argentina
description An important issue to be considered when studying a new drug for treatment of central nervous system (CNS) diseases is its ability to cross the blood–brain barrier (BBB) and distribute throughout the brain. As cerebrospinal fluid (CSF) has demonstrated to be an invaluable reservoir to study CNS availability of therapeutic proteins, we have developed an improved method for CSF sampling from the cisterna magna of rats. The technique enables the simple and rapid collection of adequate quantities (50–75 μl) of blood-free CSF, rendering a high percentage of animal survival (99%) without clinic or neurological consequences. Its success in avoiding blood contamination of CSF lays in the use of a mixture of lidocaine/ephinephrine topically injected in the rat's suboccipital area and neck. Another relevant feature of the methodology is its low cost, since the puncture device can be easily assembled with cheap and available materials and, more importantly, neither expensive stereotaxic equipment nor frame is required. The present method is demonstrated by studying the CSF pharmacokinetics of recombinant human erythropoietin (rhEPO), a well-studied therapeutic candidate for neurological diseases. Moreover, we applied this technique to evaluate a strategy of osmotic disruption of the BBB to achieve a faster delivery of rhEPO into the CNS.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/6392
Ceaglio, Natalia Analia; Orozco, Gustavo; Etcheverrigaray, Marina; Mattio, Mónica Cristina; Kratje, Ricardo Bertoldo; et al.; High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier; Elsevier; Journal of Neuroscience Methods; 219; 1; 9-2013; 70-75
0165-0270
url http://hdl.handle.net/11336/6392
identifier_str_mv Ceaglio, Natalia Analia; Orozco, Gustavo; Etcheverrigaray, Marina; Mattio, Mónica Cristina; Kratje, Ricardo Bertoldo; et al.; High performance collection of cerebrospinal fluid in rats: evaluation of erythropoietin penetration after osmotic opening of the blood-brain barrier; Elsevier; Journal of Neuroscience Methods; 219; 1; 9-2013; 70-75
0165-0270
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0165027013002471
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jneumeth.2013.07.009
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.25844

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