ArticleMolecular therapy : the journal of the American Society of Gene Therapy2006
The "perivascular pump" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 2 of them syntheses that pooled it.
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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
170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 306 citations in OpenAlex.
- The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis.Frontiers in neuroscience · 2023Pooled it
- Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration.Neurology · 2022Pooled it
- High frame ratebioRxiv : the preprint server for biology · 2026Article
- No evidence of major integrative brain clearance impairment in an Alzheimer´s disease model of transgenic APPswe/PS1dE9 mice.Fluids and barriers of the CNS · 2026Article
- Characterization of Arterial and Sinus Blood Flow Dynamics in the Rat Brain Using Phase-Contrast MRI.Annals of biomedical engineering · 2026Article
- Neurovascular Signaling in the Perivascular Space: Biophysical Principles and Disruption in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Review
- In-silico solute transport via perivascular networks in the human intracranial space.Nature communications · 2026Article
- Imaging of intranasal drug delivery to the brain: updated review 2.0.Drug delivery and translational research · 2026Review
- Infra-slow (<0.1 Hz) Modulation of Human Brain Pulsations in Awake and Sleep States.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Clinical GDNF delivery methods for Parkinson's disease.Journal of Parkinson's disease · 2026Review
- The glymphatic system and glioblastoma.Brain : a journal of neurology · 2026Review
- The myodural bridge complex: a comprehensive review of morphology, physiology, developmental biology and pathology.Frontiers in medicine · 2026Review
- MR-Guidance of Gene Therapy for Brain Diseases: Moving From Palliative Treatment to Cures.Journal of magnetic resonance imaging : JMRI · 2025Review
- Dynamics of brain valves: ostensible rectification mechanisms for cerebrospinal fluid flow.Journal of the Royal Society, Interface · 2025Article
- Alterations in MRI-visible perivascular spaces precede dementia diagnosis by 18 years in autosomal dominant Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Perivascular interactions and tissue properties modulate directional glymphatic transport in the brain.Fluids and barriers of the CNS · 2025Article
- Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- The glymphatic system was impaired in spontaneously hypertensive rats.Scientific reports · 2025Article
- The Role of the Glymphatic System in Cervical Spondylotic Myelopathy: Insights From Advanced Imaging.Clinical spine surgery · 2025Article
- Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood-brain barrier.Exploration (Beijing, China) · 2025Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
We investigated the movement of interstitially infused macromolecules within the central nervous system (CNS) in rats with high and low blood pressure (BP)/heart rate and in rats euthanized immediately before infusion (no heart action). Adeno-associated virus 2 (AAV2), fluorescent liposomes, or bovine serum albumin was infused into rat striatum (six hemispheres per group) by convection-enhanced delivery (CED). After infusion, distribution volumes were evaluated. The rats with high BP/heart rate displayed a significantly larger distribution of the infused molecules within the injected site and more extensive transport of those molecules to the globus pallidus. This difference was particularly apparent for AAV2, for which a 16.5-fold greater distribution of viral capsids was observed in the rats with high BP/heart rate than in the rats with no heartbeat. Similar results were observed for liposomes, despite their larger diameter. The distribution of all infused molecules in all rats that had low or no blood flow was confined to the space around brain blood vessels. These findings show that fluid circulation within the CNS through the perivascular space is the primary mechanism by which viral particles and other therapeutic agents administered by CED are spread within the brain and that cardiac contractions power this process.
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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.