Synergistic Effect of Cold Mannitol and Na+/Ca2+ Exchange Blocker on Blood–Brain Barrier Opening
Abstract
The precise mechanism of reversible opening of the blood-brain barrier (BBB) is elusive. Hyperosmotic mannitol at 1.4 to 1.6 M is commonly used for this purpose but intraarterial injection of such a hyperosmotic solution is known to have possible side effects on the brain. Cooling of the solution has recently been reported to have potential to open the BBB. The in situ brain perfusion technique with [(14)C]-sucrose was used first to quantify BBB permeability in rats after intraarterial injection of 1.1 M mannitol, which is less hyperosmotic than commonly used mannitol, at room temperature and at 4 degrees C. Mannitol at 4 degrees C produced an opening of the BBB but the duration of the opening was less than 30 min. We then investigated the effect of an Na(+)/Ca(2+) exchange blocker (KB-R7943) on this hypothermic BBB opening. KB-R7943 extended the BBB opening to 30 min without affecting the peak level of BBB permeability at 5 min. Simple manipulation of temperature can thus enhance the reversible BBB opening in mannitol and pharmacological manipulation of calcium dynamics works synergistically with hypothermic mannitol.
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Mannitol-mediated BBB disruption is temporary and reversible; BBB permeability peaks 5 min after intra-arterial infusion and lasts 20-30 min.
“As the mannitol-mediated BBB disruption is temporary and reversible, the BBB permeability peaks 5 min after intra-arterial (IA) infusion and lasts for 20–30 min [131, 132].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [131]
Intravenous infusion of 25% mannitol solution 15-20 min before scAAV2 vector administration can increase up to tenfold vector dispersion in mouse brain.
“Fu and colleagues first report that intravenous infusion of 25% mannitol solution 15–20 min before scAAV2 vector administration can increase up to tenfold of vector dispersion in mouse brain.”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [131]
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- Authors
- Ikeda, M., Bhattacharjee, A. K., Kondoh, T., Nagashima, T., & Tamaki, N.
- Affiliations
- Kobe University (JP)
- Corresponding author
- Kondoh, Takeshi
- ORCID
- Kondoh, Takeshi
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 291
- Issue
- 3
- Pages
- 669-674
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2068892466
- Cited by
- 62
- References
- 19
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- blood-brain barrier opening, mannitol, KB-R7943, hypothermia, blood-brain barrier permeability, calcium dynamics, synergistic effect, intra-arterial injection
- MeSH terms
- Animals, Arteries, Blood-Brain Barrier, Brain, Cold Temperature, Drug Synergism, Hypertonic Solutions, Infusions, Intra-Arterial, Kinetics, Male, Mannitol, Sucrose, Thiourea, Rats, Sprague-Dawley, Sodium-Calcium Exchanger, Rats
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