The second phase of brain trauma can be controlled by nutraceuticals that suppress DAMP-mediated microglial activation
INTRODUCTION: A delayed second wave of brain trauma is mediated in large part by microglia that are activated to a pro-inflammatory M1 phenotype by DAMP proteins released by dying neurons. These microglia can promote apoptosis or necrosis in neighboring neurons by producing a range of pro-inflammatory cytokines and the deadly oxidant peroxynitrite. This second wave could therefore be mitigated with agents that blunt the post-traumatic M1 activation of microglia and that preferentially promote a pro-healing M2 phenotype.
AREAS COVERED: The literature on nutraceuticals that might have clinical potential in this regard.
EXPERT OPINION: The chief signaling pathway whereby DAMPs promote M1 microglial activation involves activation of toll-like receptor 4 (TLR4), NADPH oxidase, NF-kappaB, and the stress activated kinases JNK and p38. The green tea catechin EGCG can suppress TLR4 expression. Phycocyanobilin can inhibit NOX2-dependent NADPH oxidase, ferulate and melatonin can oppose pro-inflammatory signal modulation by NADPH oxidase-derived oxidants. Long-chain omega-3 fatty acids, the soy isoflavone genistein, the AMPK activator berberine, glucosamine, and ketone bodies can down-regulate NF-kappaB activation. Vitamin D activity can oppose JNK/p38 activation. A sophisticated program of nutraceutical supplementation may have important potential for mitigating the second phase of neuronal death and aiding subsequent healing.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Expert review of neurotherapeutics - 21(2021), 5 vom: 04. Mai, Seite 559-570 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McCarty, Mark F [VerfasserIn] |
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| Links: |
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| Themen: |
Brain trauma |
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| Anmerkungen: |
Date Completed 28.01.2022 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/14737175.2021.1907182 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323058663 |
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| 100 | 1 | |a McCarty, Mark F |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The second phase of brain trauma can be controlled by nutraceuticals that suppress DAMP-mediated microglial activation |
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| 500 | |a Date Completed 28.01.2022 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: A delayed second wave of brain trauma is mediated in large part by microglia that are activated to a pro-inflammatory M1 phenotype by DAMP proteins released by dying neurons. These microglia can promote apoptosis or necrosis in neighboring neurons by producing a range of pro-inflammatory cytokines and the deadly oxidant peroxynitrite. This second wave could therefore be mitigated with agents that blunt the post-traumatic M1 activation of microglia and that preferentially promote a pro-healing M2 phenotype | ||
| 520 | |a AREAS COVERED: The literature on nutraceuticals that might have clinical potential in this regard | ||
| 520 | |a EXPERT OPINION: The chief signaling pathway whereby DAMPs promote M1 microglial activation involves activation of toll-like receptor 4 (TLR4), NADPH oxidase, NF-kappaB, and the stress activated kinases JNK and p38. The green tea catechin EGCG can suppress TLR4 expression. Phycocyanobilin can inhibit NOX2-dependent NADPH oxidase, ferulate and melatonin can oppose pro-inflammatory signal modulation by NADPH oxidase-derived oxidants. Long-chain omega-3 fatty acids, the soy isoflavone genistein, the AMPK activator berberine, glucosamine, and ketone bodies can down-regulate NF-kappaB activation. Vitamin D activity can oppose JNK/p38 activation. A sophisticated program of nutraceutical supplementation may have important potential for mitigating the second phase of neuronal death and aiding subsequent healing | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Brain trauma | |
| 650 | 4 | |a damp-mediated microglial activation | |
| 650 | 4 | |a neuronal death | |
| 650 | 4 | |a nutraceuticals | |
| 650 | 4 | |a peroxynitrite | |
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| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
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