ArticleStroke2015
IL-4 Is Required for Sex Differences in Vulnerability to Focal Ischemia in Mice.
Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 100 citations in OpenAlex.
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- Restricting Synaptotagmin-3 Internalization Mitigates Cerebral Ischemia/Reperfusion Injury by Curtailed Neuronal Apoptosis and Microglial Re-Programming.CNS neuroscience & therapeutics · 2026Article
- Exploring Sex Differences in Stroke Outcomes: A Comprehensive Analysis From the SPAN 1 Trial.Journal of the American Heart Association · 2026Article
- Interleukin 13 signaling modulates dopaminergic functions and nicotine reward in rodents.Molecular psychiatry · 2026Article
- Sex-Dependent Regional Vulnerability and Recovery Mechanisms in a Mouse Model of Transient Global Cerebral Ischemia.Neuromolecular medicine · 2025Article
- Knockdown of SESN2 Exacerbates Cerebral Ischemia-Reperfusion Injury Through Enhancing Glycolysis via the mTOR/HIF-1α Pathway.CNS neuroscience & therapeutics · 2025Article
- Mitochondria-associated endoplasmic reticulum membranes tethering protein VAPB-PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy.CNS neuroscience & therapeutics · 2024Article
- Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway.CNS neuroscience & therapeutics · 2024Article
- Out of the core: the impact of focal ischemia in regions beyond the penumbra.Frontiers in cellular neuroscience · 2024Review
- Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals.Frontiers in neurology · 2024Article
- Acute brain injury and nanomedicine: sex as a biological variable.Frontiers in biomaterials science · 2024Article
- Various Forms of Programmed Cell Death Are Concurrently Activated in the Population of Retinal Ganglion Cells after Ischemia and Reperfusion.International journal of molecular sciences · 2023Article
- Sex differences in the inflammatory response to stroke.Seminars in immunopathology · 2023Review
- Dual role of Apolipoprotein D as long-term instructive factor and acute signal conditioning microglial secretory and phagocytic responses.Frontiers in cellular neuroscience · 2023Article
- Regulation of microglia polarization after cerebral ischemia.Frontiers in cellular neuroscience · 2023Review
- Immune regulation based on sex differences in ischemic stroke pathology.Frontiers in immunology · 2023Review
- Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia.Biomolecules · 2022Review
- Interleukin-4 promotes microglial polarization toward a neuroprotective phenotype after retinal ischemia/reperfusion injury.Neural regeneration research · 2022Article
- Female-specific neuroprotection after ischemic stroke by vitronectin-focal adhesion kinase inhibition.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- The Effect of a NewMolecules (Basel, Switzerland) · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeInterleukin (IL)-4 protects from middle cerebral artery occlusion in male mice. Females generally show less injury in response to the same ischemic challenge, but the underlying mechanisms are not fully understood. We tested the importance of IL-4 in female protection using IL-4 knockout (KO) mice.
methodsIL-4 KO and wild-type (WT) mice of both sexes were subjected to middle cerebral artery occlusion. Infarct volume was assessed by triphenyltetrazolium chloride staining and neurobehavioral outcome by neuroscore. T cell proliferation was assessed after Concanavalin A exposure. Ischemic brain immune cell populations were analyzed by fluorescence-activated cell sorting and immunostaining.
resultsInfarction in WT females during estrus and proestrus phases was significantly smaller than in males; neurological score was better. Infarction volume was larger and neurological score worse in IL-4 KO compared with WT in both sexes, with no sex difference. Proliferation of T cells was inhibited in WT females with higher proliferation and no sex difference in IL-4 KO. Macrophage numbers and total T cells in the ischemic hemisphere were lower in WT females, and monocytes increased markedly in IL-4 KOs with no sex difference. The reduced macrophage infiltration in WT-females was predominantly M2. Loss of IL-4 increased CD68+ and iNOS+ cells and reduced YM1+ and Arg1+ cells in both sexes.
conclusionsIL-4 is required for female neuroprotection during the estrus phase of the estrus cycle. Protected WT females show a predominance of M2-activated microglia/macrophages and reduced inflammatory infiltration. Increasing macrophage M2 polarization, with or without added inhibition of infiltration, may be a new approach to stroke treatment.
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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.