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Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxi...

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Autores principales: Fernández-Serra, Rocío, Martínez-Alonso, Emma, Alcázar, Alberto, Chioua, Mourad, Marco-Contelles, José, Martínez-Murillo, Ricardo, Ramos, Milagros, Guinea, Gustavo V., González-Nieto, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266990/
https://www.ncbi.nlm.nih.gov/pubmed/35806455
http://dx.doi.org/10.3390/ijms23137449
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author Fernández-Serra, Rocío
Martínez-Alonso, Emma
Alcázar, Alberto
Chioua, Mourad
Marco-Contelles, José
Martínez-Murillo, Ricardo
Ramos, Milagros
Guinea, Gustavo V.
González-Nieto, Daniel
author_facet Fernández-Serra, Rocío
Martínez-Alonso, Emma
Alcázar, Alberto
Chioua, Mourad
Marco-Contelles, José
Martínez-Murillo, Ricardo
Ramos, Milagros
Guinea, Gustavo V.
González-Nieto, Daniel
author_sort Fernández-Serra, Rocío
collection PubMed
description Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.
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spelling pubmed-92669902022-07-09 Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations Fernández-Serra, Rocío Martínez-Alonso, Emma Alcázar, Alberto Chioua, Mourad Marco-Contelles, José Martínez-Murillo, Ricardo Ramos, Milagros Guinea, Gustavo V. González-Nieto, Daniel Int J Mol Sci Article Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies. MDPI 2022-07-04 /pmc/articles/PMC9266990/ /pubmed/35806455 http://dx.doi.org/10.3390/ijms23137449 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fernández-Serra, Rocío
Martínez-Alonso, Emma
Alcázar, Alberto
Chioua, Mourad
Marco-Contelles, José
Martínez-Murillo, Ricardo
Ramos, Milagros
Guinea, Gustavo V.
González-Nieto, Daniel
Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title_full Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title_fullStr Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title_full_unstemmed Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title_short Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations
title_sort postischemic neuroprotection of aminoethoxydiphenyl borate associates shortening of peri-infarct depolarizations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266990/
https://www.ncbi.nlm.nih.gov/pubmed/35806455
http://dx.doi.org/10.3390/ijms23137449
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