Drug transport in brain via the cerebrospinal fluid.
Open accessAbstract
The human brain has no lymphatic system, but produces over a half-liter each day of cerebrospinal fluid. The cerebrospinal fluid is secreted at the choroid plexus and occupies the cavities of the four ventricles, as well as the cranial and spinal sub-arachnoid space. The cerebrospinal fluid moves over the surfaces of the brain and spinal cord and is rapidly absorbed into the general circulation. The choroid plexus forms the blood-cerebrospinal fluid barrier, and this barrier is functionally distinct from the brain microvascular endothelium, which forms the blood-brain barrier. Virtually all non-cellular substances in blood distribute into cerebrospinal fluid, and drug entry into cerebrospinal fluid is not an index of drug transport across the blood-brain barrier. Drug injected into the cerebrospinal fluid rapidly moves into the blood via bulk flow, but penetrates into brain tissue poorly owing to the limitations of diffusion. Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium.
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The human brain microvasculature is composed of an estimated ∼100 billion capillaries, with a combined surface area of ∼20 m2 and a total length of ∼400 miles.
“Once injected, the neuralnanorobots would have access to the dense microvasculature of human brain, which is composed of an estimated ∼100 billion capillaries, with a combined surface area of ∼20 m2 and a total length of ∼400 miles.”
From Human Brain/Cloud Interface (2019) · cites this paper as Pardridge, 2011
The Introduction’s “Anatomical considerations” section reports more than 100 billion capillaries in the human brain with a total length of approximately 400 miles. It says the capillary endothelium has a much larger surface area than the choroid plexus, but does not give the claimed figure of approximately 20 m². No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIntercapillary distances in the brain are typically ∼40 μm.
“Intercapillary distances in the brain are typically ∼40 μm.”
From Human Brain/Cloud Interface (2019) · cites this paper as Pardridge, 2011
Each individual neuron within the human brain is at most 2-3 neurons away from a microcapillary.
“Hence, each individual neuron within the human brain is at most 2–3 neurons away from a microcapillary (Pardridge, 2011).”
From Human Brain/Cloud Interface (2019) · cites this paper as Pardridge, 2011
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References 21 · Cited by 316
Research works printed but not linked: 19
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- Authors
- Pardridge, W. M.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Pardridge, William M
- ORCID
- Pardridge, William M
- Venue
- Fluids and Barriers of the CNS
- Published
- 2011-01-18
- Volume
- 8
- Issue
- 1
- Pages
- 7-7
- ISSN
- 2045-8118 (ISSN-L)
- PMC
- PMC3042981
- OpenAlex
- W2106493886
- Cited by
- 316
- References
- 21
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 24 · 2023: 26 · 2022: 35 · 2021: 25 · 2020: 23 · 2019: 22 · 2018: 27 · 2017: 19 · 2016: 15 · 2015: 18 · 2014: 16 · 2013: 5 · 2012: 13
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Fluids and Barriers of the CNS (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- cerebrospinal fluid, drug transport, choroid plexus, blood-CSF barrier, blood-brain barrier, brain microvascular endothelium, bulk flow, subarachnoid space
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