The second phase of brain trauma can be controlled by nutraceuticals that suppress DAMP-mediated microglial activation. (4th May 2021)

• Record Type: Journal Article
• Authors: McCarty, Mark F.; Lerner, Aaron
• Is Part Of: Expert review of neurotherapeutics. Volume 21:Number 5(2021)
• Page Start: 559
• Page End: 570
• Publication Date: 2021-05-04
• Subjects: Brain trauma -- neuronal death -- damp-mediated microglial activation -- peroxynitrite -- nutraceuticals; Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1080/14737175.2021.1907182
• Languages: English
• ISSNs: 1473-7175

Abstract

ABSTRACT: 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.