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28-02-2023 | Stroke | Research

Delayed Chronic Acidic Postconditioning Improves Poststroke Motor Functional Recovery and Brain Tissue Repair by Activating Proton-Sensing TDAG8

Authors: Yan-Ying Fan, Yu Li, Xiao-Ying Tian, Ying-Jing Wang, Jing Huo, Bao-Lu Guo, Ru Chen, Cai-Hong Yang, Yan Li, Hui-Feng Zhang, Bao-Long Niu, Ming-Sheng Zhang

Published in: Translational Stroke Research

Abstract

Acidic postconditioning by transient CO₂ inhalation applied within minutes after reperfusion has neuroprotective effects in the acute phase of stroke. However, the effects of delayed chronic acidic postconditioning (DCAPC) initiated during the subacute phase of stroke or other acute brain injuries are unknown. Mice received daily DCAPC by inhaling 5%/10%/20% CO₂ for various durations (three cycles of 10- or 20-min CO₂ inhalation/10-min break) at days 3–7, 7–21, or 3–21 after photothrombotic stroke. Grid-walk, cylinder, and gait tests were used to assess motor function. DCAPC with all CO₂ concentrations significantly promoted motor functional recovery, even when DCAPC was delayed for 3–7 days. DCAPC enhanced the puncta density of GAP-43 (a marker of axon growth and regeneration) and synaptophysin (a marker of synaptogenesis) and reduced the amoeboid microglia number, glial scar thickness and mRNA expression of CD16 and CD32 (markers of proinflammatory M1 microglia) compared with those of the stroke group. Cerebral blood flow (CBF) increased in response to DCAPC. Furthermore, the mRNA expression of TDAG8 (a proton-activated G-protein-coupled receptor) was increased during the subacute phase of stroke, while DCAPC effects were blocked by systemic knockout of TDAG8, except for those on CBF. DCAPC reproduced the benefits by re-expressing TDAG8 in the peri-infarct cortex of TDAG8-/- mice infected with HBAAV2/9-CMV-TDAG8-3flag-ZsGreen. Taken together, we first showed that DCAPC promoted functional recovery and brain tissue repair after stroke with a wide therapeutic time window of at least 7 days after stroke. Brain-derived TDAG8 is a direct target of DCAPC that induces neuroreparative effects.

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Title: Delayed Chronic Acidic Postconditioning Improves Poststroke Motor Functional Recovery and Brain Tissue Repair by Activating Proton-Sensing TDAG8
Authors: Yan-Ying Fan
Yu Li
Xiao-Ying Tian
Ying-Jing Wang
Jing Huo
Bao-Lu Guo
Ru Chen
Cai-Hong Yang
Yan Li
Hui-Feng Zhang
Bao-Long Niu
Ming-Sheng Zhang
Publication date: 28-02-2023
Publisher: Springer US
Keyword: Stroke
Published in: Translational Stroke Research
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-023-01143-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Delayed Chronic Acidic Postconditioning Improves Poststroke Motor Functional Recovery and Brain Tissue Repair by Activating Proton-Sensing TDAG8

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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