ArticleMilitary Medical Research2025
Decreased IL-33 in the brain following repetitive mild traumatic brain injury contributes to cognitive impairment by inhibiting microglial phagocytosis.
Article in Military Medical Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed.
- MERTK-related engulfment of norepinephrinergic neuronal presynaptic membrane by astrocytes following acute TBI and potentiation effect of peripheral nerve modulation.Annals of medicine · 2026Article
- IL-33/ST2 Signaling and Microglial Functional-State Transitions After Spinal Cord Injury: Direct Evidence and Mechanistic Hypotheses.International journal of molecular sciences · 2026Review
- IL-33/ST2 Signaling Sustains Hepato-Intestinal Homeostasis by Orchestrating Vascular Surveillance and Immune Regulatory Circuits During Experimental Trypanosoma cruzi Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting IL-33 in Precision Neuroimmunology: Cellular Mechanisms and Therapeutic Strategies for CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Microglia-specific NLRP3 inhibition mitigates hippocampal neuroinflammation and cognitive deficits after hemorrhagic shock with resuscitation.Behavioral and brain functions : BBF · 2026Article
- Gasdermin D-Mediated Release of IL-33 Results in Fetal Brain Developmental Abnormalities During Maternal Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identifying Predictive Biomarkers and Immune Infiltration Features in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Intrathecal injection of 3D-mesenchymal stem cells attenuates disseminated neuroinflammation and improves cognitive function in controlled cortical impact rats.Frontiers in neuroscience · 2026Article
- MRI-DTI contributes to evaluating diffuse neural injury following repetitive mild traumatic brain injury.iScience · 2025Article
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14 authors.
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Abstract
backgroundRepetitive mild traumatic brain injury (rmTBI) is a significant risk factor for neurodegeneration, characterized by pathological protein deposition and persistent neuroinflammation. Research has observed increased interleukin-33 (IL-33) levels in the peripheral blood of patients with rmTBI, suggesting IL-33 may participate in regulating the pathological development of rmTBI. The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI, and to explore its potential as a therapeutic target to improve the neurological outcome.
methodsThe study employed an rmTBI mouse model using the wild-type (WT) and IL-33 knockout mice. Cognitive function was assessed via the Y-maze and Barnes tests. The main cell type expressing IL-33 and its receptor, suppression of tumorigenicity 2 (ST2), was then investigated in the mouse brain through immunofluorescence colocalization. As the primary neural cell responsible for ST2 expression, microglia were studied in vitro using the BV2 cell line. The effects of lipid droplets (LDs) accumulation and amyloid-beta (Aβ) phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells' phagocytosis. Additionally, HT22 neuronal apoptosis was assessed by flow cytometry. Finally, the cognitive effects of intranasal administration of IL-33 were evaluated in mice.
resultsIL-33KO mice exhibited pronounced cognitive impairment after rmTBI. In the mouse brain, astrocytes were identified as the primary source of IL-33 secretion, while microglia predominantly expressed ST2. Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function. IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβ phagocytosis in vitro. In addition, the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage. Furthermore, intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.
conclusionsDysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage. IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
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