ArticleJournal of neuroinflammation2023
Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Capillary stalling: A common microvascular pathway to stroke susceptibility and poor recovery.Neurobiology of disease · 2026Review
- M2 macrophage-derived exosomes delivering haptoglobin and interleukin-10 plasmids for synergistic therapy of intracerebral hemorrhage.Bioactive materials · 2026Article
- Age-dependent neuroinflammatory effects of red blood cells and their exosomes in a human brain-on-chip model.Blood red cells & iron · 2026Article
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- Assessing cerebral capillary function and stalling using single capillary reporters in ultrasound localization microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cerebral microhemorrhages in a mouse model of sickle cell disease.Journal of sickle cell disease · 2026Article
- Emerging Therapeutic Strategies in Intracerebral Hemorrhage: Enhancing Neurogenesis and Functional Recovery.MedComm · 2025Review
- Micro-Embolic Events and Their Clearing in the Brain. A Narrative Review.Acta physiologica (Oxford, England) · 2025Review
- Effects of iron accumulation and its chelation on oxidative stress in intracortical implants.Acta biomaterialia · 2025Article
- Traumatic brain injury persistently increases the incidence of both ischemic and hemorrhagic strokes: Potential mechanisms.Progress in neurobiology · 2025Review
- Brain endothelial cells as phagocytes: mechanisms and implications.Fluids and barriers of the CNS · 2025Review
- Examining Erythrocytes as Potential Blood Biomarkers for Autism Spectrum Disorder: Their Relationship to Symptom Severity and Adaptive Behavior.Biomedicines · 2024Article
- Hepatic LRP-1 plays an important role in amyloidosis in Alzheimer's disease mice: Potential role in chronic heavy alcohol feeding.Neurobiology of disease · 2024Article
- Deformability of Heterogeneous Red Blood Cells in Aging and Related Pathologies.Aging and disease · 2024Review
- Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke.Frontiers in nutrition · 2024Article
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC-brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.
methodsRBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC-brain endothelial interactions associated with oxidatively stressed RBC. Their relationship with microglial activation and CMH was examined with post-mortem histology.
resultsOxidatively stressed RBC stall significantly and rapidly in cerebral vessels in mice, accompanied by decreased blood flow velocity which recovers at 5 days. Post-mortem histology confirms significantly greater RBC-cerebral endothelial interactions and microglial activation at 24 h after t-BHP-treated RBC injection, which persist at 7 days. Furthermore, significant CMH develop in the absence of blood-brain barrier leakage after t-BHP-RBC injection.
conclusionsOur in vivo and ex vivo findings show the stalling and clearance of oxidatively stressed RBC in cerebral capillaries, highlighting the significance of microglial responses and altered RBC-brain endothelial interactions in CMH development. Our study provides novel mechanistic insight into CMH associated with pathological conditions with increased RBC-brain endothelial interactions.
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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.