ArticleThe Journal of clinical investigation2021
Exogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting Microglial C5aR1 with PMX205 Attenuates Neuroinflammation and Improves Neurological Recovery After Intracerebral Hemorrhage.Neurochemical research · 2026Article
- Early alveolar molecular signatures after cardiopulmonary resuscitation: a bronchoalveolar lavage (BALF) proteomic study in swine.Resuscitation plus · 2026Article
- Therapeutic Delivery of Phloretin by Mixed Emulsifier-Stabilized Nanoemulsion Alleviated Cerebral Ischemia/Reperfusion Injury.Pharmaceutics · 2025Article
- Inter-alpha Inhibitor Proteins Modulate Microvascular Endothelial Components and Cytokines After Exposure to Hypoxia-Ischemia in Neonatal Rats.Molecular neurobiology · 2025Article
- Enhanced Small Extracellular Vesicle Uptake by Activated Interneurons Improves Stroke Recovery in Mice.Journal of extracellular biology · 2025Article
- Examination of Inter-α Inhibitor Proteins in Permanent and Transient Focal Ischemia.Journal of the American Heart Association · 2025Article
- Identification of stroke biomarkers using proteomic profiling of extracellular vesicles derived from human blood: a preliminary study.Frontiers in neurology · 2025Article
- Loss of coordination between basic cellular processes in human aging.Nature aging · 2024Article
- Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Association between decreased cord blood inter-alpha inhibitor levels and neonatal encephalopathy at birth.Early human development · 2024Article
- TSG-6-Mediated Extracellular Matrix Modifications Regulate Hypoxic-Ischemic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome.Gut microbes · 2023Article
- The Polyanionic Drug Suramin Neutralizes Histones and Prevents Endotheliopathy.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Inter-Alpha Inhibitor Proteins Modify the Microvasculature after Exposure to Hypoxia-Ischemia and Hypoxia in Neonatal Rats.International journal of molecular sciences · 2023Article
- Mitochondria-containing extracellular vesicles (EV) reduce mouse brain infarct sizes and EV/HSP27 protect ischemic brain endothelial cultures.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia-Ischemia-Related Brain Injury in Neonatal Rats.International journal of molecular sciences · 2022Article
- Inter-alpha Inhibitor Proteins Ameliorate Brain Injury and Improve Behavioral Outcomes in a Sex-Dependent Manner After Exposure to Neonatal Hypoxia Ischemia in Newborn and Young Adult Rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Inter-alpha-trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk, activity, and treatment outcomes of rheumatoid arthritis.Journal of clinical laboratory analysis · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading to neutralization of histone-associated cytotoxicity in models of sepsis. Many of these detrimental processes also play critical roles in the pathophysiology of ischemic stroke. In this study, we first assessed the clinical relevance of IAIPs in stroke and then tested the therapeutic efficacy of exogenous IAIPs in several experimental stroke models. IAIP levels were reduced in both ischemic stroke patients and in mice subjected to experimental ischemic stroke when compared with controls. Post-stroke administration of IAIP significantly improved stroke outcomes across multiple stroke models, even when given 6 hours after stroke onset. Importantly, the beneficial effects of delayed IAIP treatment were observed in both young and aged mice. Using targeted gene expression analysis, we identified a receptor for complement activation, C5aR1, that was highly suppressed in both the blood and brain of IAIP-treated animals. Subsequent experiments using C5aR1-knockout mice demonstrated that the beneficial effects of IAIPs are mediated in part by C5aR1. These results indicate that IAIP is a potential therapeutic candidate for the treatment of ischemic stroke.
Indexed as
Identifiers
What OpenQuestion holds
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.