Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke

Autores
Belayev, Ludmila; Hong, Sung-Ha; Menghani, Hemant; Marcell, Shawn J.; Obenaus, Andre; Freitas, Raul S.; Khoutorova, Larissa; Balaszczuk, Veronica; Jun, Bokkyoo; Oriá, Reinaldo B.; Bazán, Gustavo Nicolás
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
Fil: Belayev, Ludmila. State University of Louisiana; Estados Unidos
Fil: Hong, Sung-Ha. State University of Louisiana; Estados Unidos
Fil: Menghani, Hemant. State University of Louisiana; Estados Unidos. University of Texas Health Science Center at Houston; Estados Unidos
Fil: Marcell, Shawn J.. State University of Louisiana; Estados Unidos
Fil: Obenaus, Andre. University of California at Irvine; Estados Unidos
Fil: Freitas, Raul S.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; Brasil
Fil: Khoutorova, Larissa. State University of Louisiana; Estados Unidos
Fil: Balaszczuk, Veronica. State University of Louisiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Jun, Bokkyoo. State University of Louisiana; Estados Unidos
Fil: Oriá, Reinaldo B.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; Brasil
Fil: Bazán, Gustavo Nicolás. State University of Louisiana; Estados Unidos
Materia
BBB
BEHAVIOR
MRI
NEUROPROTECTION
OMEGA-3 FATTY ACIDS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/139446
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/139446
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic StrokeBelayev, LudmilaHong, Sung-HaMenghani, HemantMarcell, Shawn J.Obenaus, AndreFreitas, Raul S.Khoutorova, LarissaBalaszczuk, VeronicaJun, BokkyooOriá, Reinaldo B.Bazán, Gustavo NicolásBBBBEHAVIORMRINEUROPROTECTIONOMEGA-3 FATTY ACIDShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.Fil: Belayev, Ludmila. State University of Louisiana; Estados UnidosFil: Hong, Sung-Ha. State University of Louisiana; Estados UnidosFil: Menghani, Hemant. State University of Louisiana; Estados Unidos. University of Texas Health Science Center at Houston; Estados UnidosFil: Marcell, Shawn J.. State University of Louisiana; Estados UnidosFil: Obenaus, Andre. University of California at Irvine; Estados UnidosFil: Freitas, Raul S.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; BrasilFil: Khoutorova, Larissa. State University of Louisiana; Estados UnidosFil: Balaszczuk, Veronica. State University of Louisiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Jun, Bokkyoo. State University of Louisiana; Estados UnidosFil: Oriá, Reinaldo B.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; BrasilFil: Bazán, Gustavo Nicolás. State University of Louisiana; Estados UnidosHumana Press2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/139446Belayev, Ludmila; Hong, Sung-Ha; Menghani, Hemant; Marcell, Shawn J.; Obenaus, Andre; et al.; Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke; Humana Press; Molecular Neurobiology; 55; 8; 8-2018; 7090-71060893-7648CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-018-1136-3info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-018-1136-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:51Zoai:ri.conicet.gov.ar:11336/139446instacron: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:34982025-09-03 09:49:52.214CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
title Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
spellingShingle Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
Belayev, Ludmila
BBB
BEHAVIOR
MRI
NEUROPROTECTION
OMEGA-3 FATTY ACIDS
title_short Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
title_full Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
title_fullStr Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
title_full_unstemmed Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
title_sort Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
dc.creator.none.fl_str_mv Belayev, Ludmila
Hong, Sung-Ha
Menghani, Hemant
Marcell, Shawn J.
Obenaus, Andre
Freitas, Raul S.
Khoutorova, Larissa
Balaszczuk, Veronica
Jun, Bokkyoo
Oriá, Reinaldo B.
Bazán, Gustavo Nicolás
author Belayev, Ludmila
author_facet Belayev, Ludmila
Hong, Sung-Ha
Menghani, Hemant
Marcell, Shawn J.
Obenaus, Andre
Freitas, Raul S.
Khoutorova, Larissa
Balaszczuk, Veronica
Jun, Bokkyoo
Oriá, Reinaldo B.
Bazán, Gustavo Nicolás
author_role author
author2 Hong, Sung-Ha
Menghani, Hemant
Marcell, Shawn J.
Obenaus, Andre
Freitas, Raul S.
Khoutorova, Larissa
Balaszczuk, Veronica
Jun, Bokkyoo
Oriá, Reinaldo B.
Bazán, Gustavo Nicolás
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BBB
BEHAVIOR
MRI
NEUROPROTECTION
OMEGA-3 FATTY ACIDS
topic BBB
BEHAVIOR
MRI
NEUROPROTECTION
OMEGA-3 FATTY ACIDS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
Fil: Belayev, Ludmila. State University of Louisiana; Estados Unidos
Fil: Hong, Sung-Ha. State University of Louisiana; Estados Unidos
Fil: Menghani, Hemant. State University of Louisiana; Estados Unidos. University of Texas Health Science Center at Houston; Estados Unidos
Fil: Marcell, Shawn J.. State University of Louisiana; Estados Unidos
Fil: Obenaus, Andre. University of California at Irvine; Estados Unidos
Fil: Freitas, Raul S.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; Brasil
Fil: Khoutorova, Larissa. State University of Louisiana; Estados Unidos
Fil: Balaszczuk, Veronica. State University of Louisiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Jun, Bokkyoo. State University of Louisiana; Estados Unidos
Fil: Oriá, Reinaldo B.. State University of Louisiana; Estados Unidos. Universidade Federal do Ceara; Brasil
Fil: Bazán, Gustavo Nicolás. State University of Louisiana; Estados Unidos
description Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
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/11336/139446
Belayev, Ludmila; Hong, Sung-Ha; Menghani, Hemant; Marcell, Shawn J.; Obenaus, Andre; et al.; Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke; Humana Press; Molecular Neurobiology; 55; 8; 8-2018; 7090-7106
0893-7648
CONICET Digital
CONICET
url http://hdl.handle.net/11336/139446
identifier_str_mv Belayev, Ludmila; Hong, Sung-Ha; Menghani, Hemant; Marcell, Shawn J.; Obenaus, Andre; et al.; Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke; Humana Press; Molecular Neurobiology; 55; 8; 8-2018; 7090-7106
0893-7648
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-018-1136-3
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-018-1136-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Humana Press
publisher.none.fl_str_mv Humana Press
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
_version_ 1842268999675543552
score 12.885934

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