ArticleGlia2019
Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits.
Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- C1-esterase Inhibitor Treatment is Associated with Immune and Vascular Pathway Modulation in PASC with Neurological Symptoms: Longitudinal Plasma Proteomics.Cellular and molecular neurobiology · 2026Trial
- Effect ofBiomedicines · 2026Article
- Prenatal psychological stress mediates vertical transmission of gut microbiome to the next generation affecting offspring depressive-like behaviors and neurotransmitter.BMC psychology · 2025Article
- The role of the RING finger protein 213 gene in Moyamoya disease.Fluids and barriers of the CNS · 2025Review
- Mendelian Randomization Estimates the Effects of Plasma and Cerebrospinal Fluid Proteins on Intelligence, Fluid Intelligence Score, and Cognitive Performance.Molecular neurobiology · 2025Article
- Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair.Bioactive materials · 2025Article
- Peripheral-central immune interactions in Parkinson's disease: insights into innate and adaptive immunity.Frontiers in molecular neuroscience · 2025Review
- C1-inhibitor to prevent intracerebral hemorrhage-related secondary brain injury.Fluids and barriers of the CNS · 2024Article
- Article
- Effects of C1-INH Treatment on Neurobehavioral Sequelae and Late Seizures After Traumatic Brain Injury in a Mouse Model of Controlled Cortical Impact.Neurotrauma reports · 2023Article
- The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.Current issues in molecular biology · 2022Review
- Phosphorylation-dependent proteome of Marcks in ependyma during aging and behavioral homeostasis in the mouse forebrain.GeroScience · 2022Article
- Glia-Selective Deletion of ComplementCancer research · 2021Article
- Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms.CNS neuroscience & therapeutics · 2021Review
- Parkinson's Disease and Impairment in Mitochondrial Metabolism: A Pathognomic Signature.Advances in experimental medicine and biology · 2021Article
- Complement Activation in the Central Nervous System: A Biophysical Model for Immune Dysregulation in the Disease State.Frontiers in molecular neuroscience · 2021Article
- Immune dysregulation in depression: Evidence from genome-wide association.Brain, behavior, & immunity - health · 2020Article
- Effects of nutraceutical intervention on serum proteins in aged rats.GeroScience · 2020Article
- Early treatment with C1 esterase inhibitor improves weight but not memory deficits in a rat model of status epilepticus.Physiology & behavior · 2019Article
- Plasminflammation-An Emerging Pathway to Bradykinin Production.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The cross-talk between blood proteins, immune cells, and brain function involves complex mechanisms. Plasma protein C1 inhibitor (C1INH) is an inhibitor of vascular inflammation that is induced by activation of the kallikrein-kinin system (KKS) and the complement system. Knockout of C1INH was previously correlated with peripheral vascular permeability via the bradykinin pathway, yet there was no evidence of its correlation with blood-brain barrier (BBB) integrity and brain function. In order to understand the effect of plasma C1INH on brain pathology via the vascular system, we knocked down circulating C1INH in wild-type (WT) mice using an antisense oligonucleotide (ASO), without affecting C1INH expression in peripheral immune cells or the brain, and examined brain pathology. Long-term elimination of endogenous C1INH in the plasma induced the activation of the KKS and peritoneal macrophages but did not activate the complement system. Bradykinin pathway proteins were elevated in the periphery and the brain, resulting in hypotension. BBB permeability, extravasation of plasma proteins into the brain parenchyma, activation of glial cells, and elevation of pro-inflammatory response mediators were detected. Furthermore, infiltrating innate immune cells were observed entering the brain through the lateral ventricle walls and the neurovascular unit. Mice showed normal locomotion function, yet cognition was impaired and depressive-like behavior was evident. In conclusion, our results highlight the important role of regulated plasma C1INH as it acts as a gatekeeper to the brain via the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.
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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.