Journal of Neuroinflammation
April 10, 2020
Jing Wu, Jianjun Yang, Yan Cao et al.
140 citations
General anesthesia induced by ketamine or sevoflurane disrupts iron metabolism, causing iron overload in hippocampal neurons and brain tissue. This iron overload triggers ferroptosis, a form of iron-dependent cell death, leading to cognitive deficits in young rats and aged mice. The iron chelator deferiprone reduces mitochondrial dysfunction, ferroptosis, and cognitive impairment. The mechanism involves NMDAR-RASD1 signaling activating DMT1, which mediates iron uptake. Disturbed iron metabolism may contribute to anesthesia-related neurotoxicity and cognitive decline.
Journal of Neuroinflammation
September 15, 2021
Yanling Zhou, Chengyu Wang, Xiaofeng Lan et al.
61 citations
Patients with treatment-resistant depression (TRD) who also experience pain show a higher antidepressant response rate and remission rate after six infusions of ketamine compared to those without pain. Before treatment, levels of inflammatory cytokines GM-CSF and IL-6 were elevated in the pain group. After ketamine, many inflammatory cytokines decreased in the pain group, while only TNF-α decreased in the non-pain group. Changes in IL-6 were linked to improvements in both pain intensity and depressive symptoms. The findings suggest that elevated inflammation contributes to individual differences in TRD patients with and without pain, and ketamine's antidepressant and analgesic effects may involve modulating inflammation.
Journal of Neuroinflammation
August 6, 2011
O'Shea Esther, Rubio Ana, Mayado Andrea et al.
28 citations
MDMA triggers a neuroinflammatory response in rat brain, increasing IL-1β and activating microglia. This study examined changes in IL-1 receptor antagonist and IL-1 receptor type I after MDMA, and the effects of a CB2 receptor agonist. MDMA increased IL-1ra levels and decreased IL-1RI expression in the hypothalamus, changes prevented by CB2 activation. IL-1RI was found on neurons, while IL-1β appeared in microglia after MDMA. A soluble form of IL-1RI worsened MDMA-induced neurotoxicity. MDMA also compromised blood-brain barrier integrity. The findings suggest IL-1β partly mediates MDMA's neurotoxic effects.
Journal of Neuroinflammation
December 1, 2011
Andrea Mayado, Elisa Torres, Maria D Gutierrez-Lopez et al.
8 citations
A low dose of MDMA given to rats 96 hours before a neurotoxic dose reduces damage to serotonin transporters and lowers elevated interleukin-1β levels while increasing interleukin-1 receptor antagonist levels. The low dose itself raises IL-1β at 3 hours and IL-1ra at 96 hours, and increases soluble IL-1 receptor type I expression. Blocking IL-1 signaling with sIL-1RI prevents this protective effect, while injecting IL-1β alone mimics the preconditioning, indicating that IL-1β is key in developing tolerance to MDMA neurotoxicity.
Journal of Neuroinflammation
April 17, 2026
Mary K Ford, Peter W Halcrow, Anna E Laird et al.
Daily cannabis use in people with HIV on antiretroviral therapy was associated with less global neurocognitive deficits and with an anti-inflammatory immunometabolic phenotype in monocyte-derived macrophages. This phenotype included a metabolic shift from glycolysis to oxidative phosphorylation, higher mitochondrial numbers, altered cytokine profiles (pro-inflammatory downregulation, anti-inflammatory upregulation), and higher brain-derived neurotrophic factor expression. Plasma biomarkers in daily cannabis users with HIV showed lower levels of growth differentiation factor 15 and soluble triggering receptor expressed on myeloid cells 2, and higher mature BDNF/precursor BDNF ratios that correlated with better cognition. Cannabis use may mitigate neurocognitive impairment by immunometabolically reprogramming macrophage function towards an anti-inflammatory and neuroprotective state.
Journal of Neuroinflammation
December 18, 2025
Mengqi Han, Bing Xie, Yuan Yu et al.
Chronic stress triggers depression by activating a gut-immune-brain pathway. In mice exposed to chronic restraint stress, gut microbiota changes caused small intestinal γδ T cells to migrate to the brain, where they released interleukin-17A (IL-17A). This IL-17A impaired a mitochondrial cleanup process called mitophagy in the hippocampus, leading to reduced energy production, damaged synapses, and depression-like behavior. Blocking γδ T cell migration, removing a key receptor on these cells, or giving the antidepressant arketamine all restored mitophagy and improved behavior. The findings identify a specific chain from gut microbes to immune cells to brain mitochondria that drives stress-induced depression, and point to arketamine as a potential treatment targeting this pathway.