Department of research, Catalytic Longevity Foundation, San Diego, California, USA.
Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Tel Hashomer, Israel.
Expert Rev Neurother. 2021 May;21(5):559-570. doi: 10.1080/14737175.2021.1907182. Epub 2021 Apr 5.
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.
The literature on nutraceuticals that might have clinical potential in this regard.
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.
由死亡神经元释放的损伤相关分子模式（DAMP）蛋白激活的小胶质细胞，很大程度上介导了脑外伤的第二波延迟发生。这些小胶质细胞通过产生一系列促炎细胞因子和致命的氧化剂过氧亚硝酸盐，促进邻近神经元的凋亡或坏死。因此，可以使用能减轻创伤后小胶质细胞 M1 激活并优先促进促修复 M2 表型的药物来减轻这种第二波损伤。
在这方面具有临床潜力的营养保健品的文献综述。
DAMP 促进 M1 小胶质细胞激活的主要信号通路涉及 Toll 样受体 4（TLR4）、NADPH 氧化酶、NF-κB、应激激活激酶 JNK 和 p38 的激活。绿茶儿茶素 EGCG 可以抑制 TLR4 的表达。藻蓝蛋白原可以抑制依赖 NADPH 氧化酶的 NOX2，阿魏酸和褪黑素可以对抗 NADPH 氧化酶衍生的氧化剂对促炎信号调节的作用。长链 ω-3 脂肪酸、大豆异黄酮染料木黄酮、AMPK 激活剂黄连素、氨基葡萄糖和酮体可以下调 NF-κB 的激活。维生素 D 活性可以对抗 JNK/p38 的激活。复杂的营养保健品补充计划可能对减轻神经元死亡的第二阶段和促进随后的愈合有重要的潜在作用。
