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Notably, as suggested in an animal model of neuroinflammation induced by ischemic stroke damage known to increase the prevalence of M1 microglia in the brain, pre-treatment with melatonin upregulated the expression of TREM2 while downregulating that of proinflammatory genes in microglia (e.g., inducible nitric oxide synthase) [101], suggesting that melatonin may polarize microglia towards its M2 phenotype

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Toxicol Appl Pharmacol 1989;101:356-69

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Both compounds require gradual dose escalation