ArticleThe Journal of pharmacology and experimental therapeutics2014
Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 111 citations in OpenAlex.
- Cerebrospinal Fluid Over Plasma Links Analytes to Cognitive Decline in Older Adults at Risk for Alzheimer's Disease.Annals of clinical and translational neurology · 2026Article
- ACKR2 aids the regulation of bone marrow eosinophils to promote monocyte differentiation and anti-bacterial immunity.Nature communications · 2026Article
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort.Molecular psychiatry · 2026Article
- The Role of CCL11-CCR3 Induced Mitochondrial Dysfunction and Oxidative Stress in Cognitive Impairment in Early-onset Schizophrenia: Insights from Preclinical Studies.Inflammation · 2025Article
- Cognitive dysfunction in schizophrenia: association with peripheral blood inflammatory signatures.BMC psychiatry · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Smaller hippocampal tail volume is associated with plasma CCL11 levels in patients with major depressive disorder.Psychological medicine · 2025Article
- Qifuyin against CCL11-Induced cognitive impairment by inhibiting microglial senescence via CCR3 signaling.Immunity & ageing : I & A · 2025Article
- Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immune control of brain physiology.Nature reviews. Immunology · 2025Review
- Association between serum chemokines levels and delayed neurocognitive recovery after non-cardiac surgery in elderly patients: a nested case-control study.Perioperative medicine (London, England) · 2025Article
- Immune dysregulation in bipolar disorder.Journal of affective disorders · 2025Article
- Senescent-like microglia limit remyelination through the senescence associated secretory phenotype.Nature communications · 2025Article
- Article
- Targeting senescent microglia in progressive multiple sclerosis: a geroscience-informed approach.Frontiers in immunology · 2025Article
- Allergy-unrelated eosinophil activation in the peripheral blood of children with neurodevelopmental disorders.Frontiers in neurology · 2025Article
- The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.Biomedicines · 2024Review
- Differences in Eotaxin Serum Levels between Polytraumatized Patients with and without Concomitant Traumatic Brain Injury-A Matched Pair Analysis.Journal of clinical medicine · 2024Article
- Blood-based therapies to combat neurodegenerative diseases.Metabolic brain disease · 2024Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.
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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.