ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2021
Interleukin-4 improves white matter integrity and functional recovery after murine traumatic brain injury via oligodendroglial PPARγ.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 84 citations in OpenAlex.
- Endothelial miR-15a/16-1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Melatonin promotes recovery from ischemic stroke by modulating microglia polarization and inhibiting oligodendrocyte pyroptosis via the RORα/AMPKα/STAT1 pathway.Journal of translational medicine · 2026Article
- Physical exercise promotes white matter repair after ischemic stroke.Neural regeneration research · 2026Article
- Discovery and Characterization of Interleukin-4-Specific Affibodies for Affinity-Controlled Protein Release and Macrophage Polarization.bioRxiv : the preprint server for biology · 2026Article
- Multifunctional Nanoparticles in Traumatic Brain Injury: From Targeted Imaging and Diagnosis to Innovative Therapeutics.International journal of nanomedicine · 2026Review
- The predictive value of serum 25(OH)D, AQP4, and IL-4 levels for edema volume and clinical prognosis after traumatic brain injury.Frontiers in medicine · 2026Article
- Cytokines and related signaling pathways in traumatic brain injury.Frontiers in immunology · 2026Review
- Article
- Interleukin-4-Enhanced Oligodendrocyte Differentiation Depends on Extracellular Zinc Uptake via ZIP11.Cells · 2025Article
- Late-Stage Activation of Toll-like receptor 3 Alleviates Cognitive Impairment and Neuropathology in an Alzheimer's Disease Mouse Model.Molecular neurobiology · 2025Article
- Traumatic Brain Injury: Novel Experimental Approaches and Treatment Possibilities.Life (Basel, Switzerland) · 2025Review
- Reversing Persistent PTEN Activation after Traumatic Brain Injury Fuels Long-Term Axonal Regeneration via Akt/mTORC1 Signaling Cascade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide.CNS & neurological disorders drug targets · 2025Review
- The Neuroprotective Mechanisms of PPAR-γ: Inhibition of Microglia-Mediated Neuroinflammation and Oxidative Stress in a Neonatal Mouse Model of Hypoxic-Ischemic White Matter Injury.CNS neuroscience & therapeutics · 2024Article
- Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.JCI insight · 2024Article
- Microglial histone deacetylase 2 is dispensable for functional and histological outcomes in a mouse model of traumatic brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia.Molecular neurobiology · 2024Article
- Interleukin-4 protects retinal ganglion cells and promotes axon regeneration.Cell communication and signaling : CCS · 2024Article
- TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia.Clinical and translational medicine · 2024Article
- A Novel Hybrid of Telmisartan and Borneol Ameliorates Neuroinflammation and White Matter Injury in Ischemic Stroke Through ATF3/CH25H Axis.Translational stroke research · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Long-term neurological recovery after severe traumatic brain injury (TBI) is strongly linked to the repair and functional restoration of injured white matter. Emerging evidence suggests that the anti-inflammatory cytokine interleukin-4 (IL-4) plays an important role in promoting white matter integrity after cerebral ischemic injury. Here, we report that delayed intranasal delivery of nanoparticle-packed IL-4 boosted sensorimotor neurological recovery in a murine model of controlled cortical impact, as assessed by a battery of neurobehavioral tests for up to five weeks. Post-injury IL-4 treatment failed to reduce macroscopic brain lesions after TBI, but preserved the structural and functional integrity of white matter, at least in part through oligodendrogenesis. IL-4 directly facilitated the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-producing oligodendrocytes in primary cultures, an effect that was attenuated by selective PPARγ inhibition. IL-4 treatment after TBI in vivo also failed to stimulate oligodendrogenesis or improve white matter integrity in OPC-specific PPARγ conditional knockout (cKO) mice. Accordingly, IL-4-afforded improvements in sensorimotor neurological recovery after TBI were markedly impaired in the PPARγ cKO mice compared to wildtype controls. These results support IL-4 as a potential novel neurorestorative therapy to improve white matter functionality and mitigate the long-term neurological consequences of TBI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.