Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway.
The international journal of neuropsychopharmacology October 1, 2024 Gargi Mandal, Madeline Kirkpatrick, Silvia Alboni et al. 12 citations
Both enantiomers of ketamine—arketamine (R-ketamine) and esketamine (S-ketamine)—prevented cytokine-induced reductions in hippocampal neurogenesis and increases in apoptosis in a fetal hippocampal progenitor cell line. The protective effects were mediated by inhibition of specific inflammatory cytokines: R-ketamine blocked IL-1β-induced production of IL-2 and IL-13, while S-ketamine blocked IL-1β-induced tumor necrosis factor-alpha. Both enantiomers also prevented IL-1β-induced activation of the neurotoxic kynurenine pathway, but neither prevented IL-6-induced kynurenine pathway activation. The findings suggest ketamine's antidepressant mechanisms involve pro-neurogenic and anti-inflammatory actions that depend on the inflammatory context.