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Review
. 2022 Mar 23:16:807911.
doi: 10.3389/fncel.2022.807911. eCollection 2022.

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

Georgios Michalettos  1 , Karsten Ruscher  1   2
Affiliations
Review

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

Georgios Michalettos et al. Front Cell Neurosci. .

Abstract

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.

Keywords: GABA; chemokine; glutamate decarboxylate; immune cell; inflammation; neurotransmission; stroke recovery.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Putative involvement of GABAergic signaling in neuro-immunological crosstalk after stroke.Following stroke, neurons, glial, and immune cells synthesize and release GABA. In addition, GABAA and GABAB receptors and specific GABA transporters are found in a number of immune and glial cells. GABA exerts anti-inflammatory effects and changes in the function of GABAceptive neurons indicated in the figure. The figure was created with Biorender.com.
See this image and copyright information in PMC

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