Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions

Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle ce...

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Autores principales:	David Couret, Cynthia Planesse, Jessica Patche, Nicolas Diotel, Brice Nativel, Steeve Bourane, Olivier Meilhac
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	high-density lipoprotein stroke acute hyperglycemia blood–brain barrier hemorrhagic transformation Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/f6a3c4cacb1e4980b54539037d1fa433
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spelling	oai:doaj.org-article:f6a3c4cacb1e4980b54539037d1fa4332021-11-11T18:23:35ZLack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions10.3390/molecules262163651420-3049https://doaj.org/article/f6a3c4cacb1e4980b54539037d1fa4332021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6365https://doaj.org/toc/1420-3049Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (<i>p</i> = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. <b>Conclusion:</b> We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity.David CouretCynthia PlanesseJessica PatcheNicolas DiotelBrice NativelSteeve BouraneOlivier MeilhacMDPI AGarticlehigh-density lipoproteinstrokeacute hyperglycemiablood–brain barrierhemorrhagic transformationOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6365, p 6365 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-density lipoprotein stroke acute hyperglycemia blood–brain barrier hemorrhagic transformation Organic chemistry QD241-441
spellingShingle	high-density lipoprotein stroke acute hyperglycemia blood–brain barrier hemorrhagic transformation Organic chemistry QD241-441 David Couret Cynthia Planesse Jessica Patche Nicolas Diotel Brice Nativel Steeve Bourane Olivier Meilhac Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
description	Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (<i>p</i> = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. <b>Conclusion:</b> We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity.
format	article
author	David Couret Cynthia Planesse Jessica Patche Nicolas Diotel Brice Nativel Steeve Bourane Olivier Meilhac
author_facet	David Couret Cynthia Planesse Jessica Patche Nicolas Diotel Brice Nativel Steeve Bourane Olivier Meilhac
author_sort	David Couret
title	Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
title_short	Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
title_full	Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
title_fullStr	Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
title_full_unstemmed	Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions
title_sort	lack of neuroprotective effects of high-density lipoprotein therapy in stroke under acute hyperglycemic conditions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f6a3c4cacb1e4980b54539037d1fa433
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Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions

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