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

Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas
  • Javier Yajeya
    University of Salamanca, School of Medicine, Department of Physiology, Spain
  • Noelia González
    Institut pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique (IDRPHT), France
  • Isabel Ruiz
    Gemacbio, France
  • Marianny Pernìa
    University of Salamanca, Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neurobiology of Hearing, Spain
  • Michel Geffard
    Gemacbio - Institut pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique (IDRPHT), France
  • Rafael Coveñas
    University of Salamanca, Institute of Neurosciences of Castilla y León (INCYL), Spain

Abstract

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, NO2-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.

Keywords

Ischemia; astrocyte; IDO pathway; monoclonal antibody; immunohistochemistry; kynurenic acid; 3-hydroxy anthranilic acid.

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Submitted: 2017-03-14 18:11:27
Published: 2017-05-25 13:37:32
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Copyright (c) 2017 Arturo Mangas, Javier Yajeya, Noelia González, Isabel Ruiz, Marianny Pernìa, Michel Geffard, Rafael Coveñas

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