Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke

<p>In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD4...

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Main Authors: Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas
Format: Article
Language:English
Published: PAGEPress Publications 2017-05-01
Series:European Journal of Histochemistry
Subjects:
Online Access:http://ejh.it/index.php/ejh/article/view/2790
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author Arturo Mangas
Javier Yajeya
Noelia González
Isabel Ruiz
Marianny Pernìa
Michel Geffard
Rafael Coveñas
author_facet Arturo Mangas
Javier Yajeya
Noelia González
Isabel Ruiz
Marianny Pernìa
Michel Geffard
Rafael Coveñas
author_sort Arturo Mangas
collection DOAJ
description <p>In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO<sub>2</sub>-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers. In the early phase (3 and 5 days of the stroke, we observed no effect of Gemst treatment (7.5 mg/day, subcutaneously for 3, 5 days). In the late phase (21 days) of stroke and exclusively in the ipsilateral side of non-treated animals an overexpression of kynurenic acid, 3-hydroxy anthranilic acid, CD45, CD11b, GFAP and ionized calcium-binding adapter molecule 1 (IBA-1) was found. In treated animals, the overexpression of the four former markers was completely abolished whereas the overexpression of the two latter ones was decreased down to normal levels. Gemst reversed the pathological conditions of stroke to normal situations. Gemst exerts a multifunctional action: down-regulates the indoleamine 2, 3-dioxygenase pathway and abolishes brain infiltration, microglial activation and gliosis. Moreover, Gemst has no effect on the expression of doublecortin, a protein involved in neuronal migration. Gemst could be a new drug for the treatment of stroke since it reverses the pathological findings of stroke and normalizes brain tissue conditions following the ischemic insult.</p>
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spelling doaj.art-c78944f5c94c430dbcc526d5e2d8f78b2022-12-22T01:49:23ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062017-05-0161210.4081/ejh.2017.27901554Gemst: a taylor-made combination that reverts neuroanatomical changes in strokeArturo Mangas0Javier Yajeya1Noelia González2Isabel Ruiz3Marianny Pernìa4Michel Geffard5Rafael Coveñas6GemacbioUniversity of Salamanca, School of Medicine, Department of PhysiologyInstitut pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique (IDRPHT)GemacbioUniversity of Salamanca, Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neurobiology of HearingGemacbio - Institut pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique (IDRPHT)University of Salamanca, Institute of Neurosciences of Castilla y León (INCYL)<p>In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO<sub>2</sub>-tyrosine) and indoleamine 2, 3-dioxygenase pathway (kynurenic acid, 3-hydroxy anthranilic acid) markers has been evaluated in early and late phases of stroke. For this purpose, we have developed eight highly specific monoclonal antibodies directed against some of these markers. In the early phase (3 and 5 days of the stroke, we observed no effect of Gemst treatment (7.5 mg/day, subcutaneously for 3, 5 days). In the late phase (21 days) of stroke and exclusively in the ipsilateral side of non-treated animals an overexpression of kynurenic acid, 3-hydroxy anthranilic acid, CD45, CD11b, GFAP and ionized calcium-binding adapter molecule 1 (IBA-1) was found. In treated animals, the overexpression of the four former markers was completely abolished whereas the overexpression of the two latter ones was decreased down to normal levels. Gemst reversed the pathological conditions of stroke to normal situations. Gemst exerts a multifunctional action: down-regulates the indoleamine 2, 3-dioxygenase pathway and abolishes brain infiltration, microglial activation and gliosis. Moreover, Gemst has no effect on the expression of doublecortin, a protein involved in neuronal migration. Gemst could be a new drug for the treatment of stroke since it reverses the pathological findings of stroke and normalizes brain tissue conditions following the ischemic insult.</p>http://ejh.it/index.php/ejh/article/view/2790IschemiaastrocyteIDO pathwaymonoclonal antibodyimmunohistochemistrykynurenic acid3-hydroxy anthranilic acid.
spellingShingle Arturo Mangas
Javier Yajeya
Noelia González
Isabel Ruiz
Marianny Pernìa
Michel Geffard
Rafael Coveñas
Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
European Journal of Histochemistry
Ischemia
astrocyte
IDO pathway
monoclonal antibody
immunohistochemistry
kynurenic acid
3-hydroxy anthranilic acid.
title Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
title_full Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
title_fullStr Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
title_full_unstemmed Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
title_short Gemst: a taylor-made combination that reverts neuroanatomical changes in stroke
title_sort gemst a taylor made combination that reverts neuroanatomical changes in stroke
topic Ischemia
astrocyte
IDO pathway
monoclonal antibody
immunohistochemistry
kynurenic acid
3-hydroxy anthranilic acid.
url http://ejh.it/index.php/ejh/article/view/2790
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