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Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery

Adaptive plasticity processes are required involving neurons as well as non-neuronal cells to recover lost brain functions after an ischemic stroke. Recent studies show that gamma-Aminobutyric acid (GABA) has profound effects on glial and immune cell functions in addition to its inhibitory actions o...

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Autores principales: Michalettos, Georgios, Ruscher, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983863/
https://www.ncbi.nlm.nih.gov/pubmed/35401118
http://dx.doi.org/10.3389/fncel.2022.807911
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author Michalettos, Georgios
Ruscher, Karsten
author_facet Michalettos, Georgios
Ruscher, Karsten
author_sort Michalettos, Georgios
collection PubMed
description Adaptive plasticity processes are required involving neurons as well as non-neuronal cells to recover lost brain functions after an ischemic stroke. Recent studies show that gamma-Aminobutyric acid (GABA) has profound effects on glial and immune cell functions in addition to its inhibitory actions on neuronal circuits in the post-ischemic brain. Here, we provide an overview of how GABAergic neurotransmission changes during the first weeks after stroke and how GABA affects functions of astroglial and microglial cells as well as peripheral immune cell populations accumulating in the ischemic territory and brain regions remote to the lesion. Moreover, we will summarize recent studies providing data on the immunomodulatory actions of GABA of relevance for stroke recovery. Interestingly, the activation of GABA receptors on immune cells exerts a downregulation of detrimental anti-inflammatory cascades. Conversely, we will discuss studies addressing how specific inflammatory cascades affect GABAergic neurotransmission on the level of GABA receptor composition, GABA synthesis, and release. In particular, the chemokines CXCR4 and CX3CR1 pathways have been demonstrated to modulate receptor composition and synthesis. Together, the actual view on the interactions between GABAergic neurotransmission and inflammatory cascades points towards a specific crosstalk in the post-ischemic brain. Similar to what has been shown in experimental models, specific therapeutic modulation of GABAergic neurotransmission and inflammatory pathways may synergistically promote neuronal plasticity to enhance stroke recovery.
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spelling pubmed-89838632022-04-07 Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery Michalettos, Georgios Ruscher, Karsten Front Cell Neurosci Cellular Neuroscience Adaptive plasticity processes are required involving neurons as well as non-neuronal cells to recover lost brain functions after an ischemic stroke. Recent studies show that gamma-Aminobutyric acid (GABA) has profound effects on glial and immune cell functions in addition to its inhibitory actions on neuronal circuits in the post-ischemic brain. Here, we provide an overview of how GABAergic neurotransmission changes during the first weeks after stroke and how GABA affects functions of astroglial and microglial cells as well as peripheral immune cell populations accumulating in the ischemic territory and brain regions remote to the lesion. Moreover, we will summarize recent studies providing data on the immunomodulatory actions of GABA of relevance for stroke recovery. Interestingly, the activation of GABA receptors on immune cells exerts a downregulation of detrimental anti-inflammatory cascades. Conversely, we will discuss studies addressing how specific inflammatory cascades affect GABAergic neurotransmission on the level of GABA receptor composition, GABA synthesis, and release. In particular, the chemokines CXCR4 and CX3CR1 pathways have been demonstrated to modulate receptor composition and synthesis. Together, the actual view on the interactions between GABAergic neurotransmission and inflammatory cascades points towards a specific crosstalk in the post-ischemic brain. Similar to what has been shown in experimental models, specific therapeutic modulation of GABAergic neurotransmission and inflammatory pathways may synergistically promote neuronal plasticity to enhance stroke recovery. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8983863/ /pubmed/35401118 http://dx.doi.org/10.3389/fncel.2022.807911 Text en Copyright © 2022 Michalettos and Ruscher. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Michalettos, Georgios
Ruscher, Karsten
Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title_full Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title_fullStr Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title_full_unstemmed Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title_short Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery
title_sort crosstalk between gabaergic neurotransmission and inflammatory cascades in the post-ischemic brain: relevance for stroke recovery
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983863/
https://www.ncbi.nlm.nih.gov/pubmed/35401118
http://dx.doi.org/10.3389/fncel.2022.807911
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