The Integrity of the Blood–Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury
Open accessAbstract
A healthy blood–brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.
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Glutamate does not readily cross the blood-brain barrier, which may limit its direct influence on brain glutamate levels.
“glutamate does not readily cross the BBB, which may limit its direct influence on brain glutamate levels.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [542]
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References 45 · Cited by 27
- Authors
- Boyko, M., Gruenbaum, B. F., Frank, D., Natanel, D., Negev, S., Azab, A. N., Barsky, G., Knyazer, B., Kofman, O., & Zlotnik, A.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Mayo Clinic (US)
- Corresponding author
- Boyko, Matthew
- Gruenbaum, Benjamin F.
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-03-20
- Volume
- 24
- Issue
- 6
- Pages
- 5897
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10056818
- OpenAlex
- W4328119335
- Cited by
- 27
- References
- 45
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 11 · 2023: 1
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ben-Gurion University of the Negev
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- blood-brain barrier, traumatic brain injury, glutamate, blood-brain barrier permeability, blood-brain barrier disruption, cerebrospinal fluid glutamate, neurotoxicity, neurodegeneration
- MeSH terms
- Brain Injuries, Traumatic, Animals, Blood-Brain Barrier, Brain, Head, Glutamic Acid, Rats
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