Post-ischemic protein restriction induces sustained neuroprotection, neurological recovery, brain remodeling, and gut microbiota rebalancing
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
BACKGROUND: Moderate dietary protein restriction confers neuroprotection when applied before ischemic stroke. How a moderately protein-reduced diet influences stroke recovery when administered after stroke, is a clinically relevant question. This question has not yet been investigated.
METHODS: Male C57BL6/J mice were exposed to transient intraluminal middle cerebral artery occlusion. Immediately after the stroke, mice were randomized to two normocaloric diets: a moderately protein-reduced diet containing 8% protein (PRD) or normal diet containing 20% protein (ND). Post-stroke neurological deficits were evaluated by a comprehensive test battery. Antioxidant and neuroinflammatory responses in the brain and liver were evaluated by Western blot and RTqPCR. Stroke-induced brain injury, microvascular integrity, glial responses, and neuroplasticity were assessed by immunohistochemistry. Fecal microbiota analysis was performed using 16S ribosomal RNA amplicon sequencing.
RESULTS: We show that PRD reduces brain infarct volume after three days and enhances neurological and, specifically, motor-coordination recovery over six weeks in stroke mice. The recovery-promoting effects of PRD were associated with increased antioxidant responses and reduced neuroinflammation. Histochemical studies revealed that PRD increased long-term neuronal survival, increased peri-infarct microvascular density, reduced microglia/macrophage accumulation, increased contralesional pyramidal tract plasticity, and reduced brain atrophy. Fecal microbiota analysis showed reduced bacterial richness and diversity in ischemic mice on ND starting at 7 dpi. PRD restored bacterial richness and diversity at these time points.
CONCLUSION: Moderate dietary protein restriction initiated post-ischemic stroke induces neurological recovery, brain remodeling, and neuroplasticity in mice by mechanisms involving antiinflammation and, in the post-acute phase, commensal gut microbiota rebalancing.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:100 |
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| Enthalten in: |
Brain, behavior, and immunity - 100(2022) vom: 15. Feb., Seite 134-144 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Silva de Carvalho, Tayana [VerfasserIn] |
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| Links: |
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| Themen: |
Dietary protein |
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| Anmerkungen: |
Date Completed 14.03.2022 Date Revised 31.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2021.11.016 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM333853237 |
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| 100 | 1 | |a Silva de Carvalho, Tayana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Post-ischemic protein restriction induces sustained neuroprotection, neurological recovery, brain remodeling, and gut microbiota rebalancing |
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| 500 | |a Date Completed 14.03.2022 | ||
| 500 | |a Date Revised 31.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Moderate dietary protein restriction confers neuroprotection when applied before ischemic stroke. How a moderately protein-reduced diet influences stroke recovery when administered after stroke, is a clinically relevant question. This question has not yet been investigated | ||
| 520 | |a METHODS: Male C57BL6/J mice were exposed to transient intraluminal middle cerebral artery occlusion. Immediately after the stroke, mice were randomized to two normocaloric diets: a moderately protein-reduced diet containing 8% protein (PRD) or normal diet containing 20% protein (ND). Post-stroke neurological deficits were evaluated by a comprehensive test battery. Antioxidant and neuroinflammatory responses in the brain and liver were evaluated by Western blot and RTqPCR. Stroke-induced brain injury, microvascular integrity, glial responses, and neuroplasticity were assessed by immunohistochemistry. Fecal microbiota analysis was performed using 16S ribosomal RNA amplicon sequencing | ||
| 520 | |a RESULTS: We show that PRD reduces brain infarct volume after three days and enhances neurological and, specifically, motor-coordination recovery over six weeks in stroke mice. The recovery-promoting effects of PRD were associated with increased antioxidant responses and reduced neuroinflammation. Histochemical studies revealed that PRD increased long-term neuronal survival, increased peri-infarct microvascular density, reduced microglia/macrophage accumulation, increased contralesional pyramidal tract plasticity, and reduced brain atrophy. Fecal microbiota analysis showed reduced bacterial richness and diversity in ischemic mice on ND starting at 7 dpi. PRD restored bacterial richness and diversity at these time points | ||
| 520 | |a CONCLUSION: Moderate dietary protein restriction initiated post-ischemic stroke induces neurological recovery, brain remodeling, and neuroplasticity in mice by mechanisms involving antiinflammation and, in the post-acute phase, commensal gut microbiota rebalancing | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Dietary protein | |
| 650 | 4 | |a Gut microbiome | |
| 650 | 4 | |a Ischemic stroke | |
| 650 | 4 | |a Middle cerebral artery occlusion | |
| 650 | 4 | |a Neuroinflammation | |
| 650 | 4 | |a Neuroplasticity | |
| 700 | 1 | |a Singh, Vikramjeet |e verfasserin |4 aut | |
| 700 | 1 | |a Mohamud Yusuf, Ayan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Schultz Moreira, Adriana R |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez-Mendoza, Eduardo H |e verfasserin |4 aut | |
| 700 | 1 | |a Sardari, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Nascentes Melo, Luiza M |e verfasserin |4 aut | |
| 700 | 1 | |a Doeppner, Thorsten R |e verfasserin |4 aut | |
| 700 | 1 | |a Kehrmann, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Scholtysik, Rene |e verfasserin |4 aut | |
| 700 | 1 | |a Hitpass, Ludger |e verfasserin |4 aut | |
| 700 | 1 | |a Gunzer, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Hermann, Dirk M |e verfasserin |4 aut | |
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