The blood–brain barrier (BBB), the interface that controls transport between the blood and the brain, does not behave uniformly across the brain, according to a new comparative study published in Fluids and Barriers of the CNS. Dysfunction of this barrier has been implicated in a range of neurological conditions, including neurodegenerative disorders, epilepsy, stroke, traumatic brain injury, and brain tumors, yet understanding of how BBB properties differ between healthy brain regions has remained limited. The new work set out to map regional variation in BBB permeability in healthy people and to examine how these measurements relate to sex and age.
The researchers retrospectively analyzed dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans from 102 healthy participants aged 19 to 85, of whom 55.8 percent were female. Using this technique, which tracks the passage of a gadolinium-based contrast agent into brain tissue, the team assessed BBB permeability and plasma volume fraction across 124 brain regions. They then examined the effects of sex and age on both measures. To complement the human imaging data, additional experiments were carried out on 11-week-old Sprague Dawley rats, combining DCE-MRI with Evans blue–based fluorescence analyses.
The results showed that BBB-related measurements varied across brain regions. In analyses referenced to the brainstem, several cortical regions, including the frontal cortex, generally showed lower permeability values than the brainstem reference, although the precise regional ordering differed before brainstem normalization was applied. Plasma volume fraction, a separate measure of the blood compartment within tissue, showed higher values in the frontal and occipital cortices than in the brainstem and white matter. The complementary rat experiments likewise demonstrated regional BBB heterogeneity, supporting the idea that these differences are not unique to humans.
The study also uncovered age-related patterns. Sex-stratified analyses revealed positive associations between age and whole-brain percent volume with a leaky BBB, normalized to plasma volume fraction, in both sexes. In other words, older participants tended to have a greater proportion of brain volume showing BBB leakage. Formal interaction analysis demonstrated that this whole-brain age association was significantly steeper in males than in females. However, when the researchers looked at individual lobes, no lobe-specific age-by-sex interaction survived correction for multiple comparisons, meaning the sex difference was established at the whole-brain level rather than in any single lobe.
The authors conclude that the study demonstrates regional heterogeneity in BBB-related measurements and suggests that BBB properties may reflect regional functional specialization of the brain. The steeper association between age and whole-brain leaky BBB volume in males stands out as a key finding. Because the human data were collected retrospectively in a healthy cohort and the animal work involved young adult rats, the findings describe patterns of variation and association rather than mechanisms or clinical outcomes, and the authors note the article is being shared early as a peer-reviewed, accepted version subject to further edits before the final Version of Record.
Subject of Research: Regional variation in blood–brain barrier permeability in healthy humans and rodents and its relationship to sex and age
Article Title: Comparative analysis of regional blood–brain barrier permeability in humans and rodents: implications for functional specialization and aging
Article References: Mirloo, S., Kamintsky, L., Cort-Samuel, S., Muradov, J., Mansoor, S., Alhadeed, L., Abu Ahmad, A., Shafiq, B., Talebanpour, A., Saar-Ashkenazy, R., Serlin, Y., & Friedman, A. (2026). Comparative analysis of regional blood–brain barrier permeability in humans and rodents: implications for functional specialization and aging. Fluids and Barriers of the CNS. https://doi.org/10.1186/s12987-026-00881-8
Image Credits: AI Generated
DOI: 10.1186/s12987-026-00881-8
Keywords: blood–brain barrier, DCE-MRI, BBB permeability, plasma volume fraction, aging, sex differences, brain regions, gadolinium contrast agent, Sprague Dawley rats, Evans blue, neurological disease, Fluids and Barriers of the CNS
News Source: Cassandra Pierce. (October 29, 2026). Blood–brain barrier permeability varies across brain regions and shifts with age. Scienmag.
