Groundbreaking discoveries from the 13th International Conference on Cerebral Vascular Biology
Imagine a security system so sophisticated that it can distinguish between life-saving medicine and harmful substances, all while protecting your most vital organ. This isn't science fiction—it's the blood-brain barrier (BBB), a remarkable biological interface that shields your brain from potential threats in the bloodstream. For decades, this protective barrier has posed both a challenge and a fascination for scientists: how does it work, and how can we safely bypass it to treat devastating neurological conditions?
Every two years, the world's leading cerebrovascular biologists gather at the International Conference on Cerebral Vascular Biology (CVB) to share their latest discoveries about this extraordinary system. The 2019 conference in Miami showcased groundbreaking research that brings us closer to understanding—and therapeutically harnessing—the brain's sophisticated defense network 1 . From revolutionary laboratory models that predict how drugs penetrate the brain to innovative technologies that visualize barrier breakdown in real-time, scientists are unraveling the BBB's secrets at an unprecedented pace. This article explores the most exciting developments from this conference and what they mean for the future of treating brain diseases.
The BBB selectively prevents harmful substances from entering the brain while allowing essential nutrients to pass through.
BBB dysfunction is implicated in Alzheimer's, stroke, multiple sclerosis, and other neurological conditions.
The blood-brain barrier is far more than just a physical barrier—it's a dynamic, multicellular structure known as the neurovascular unit:
These specialized cells form the wall of brain blood vessels, fitting together so tightly that they prevent most substances from passing between them.
These cells wrap around capillaries, providing structural support and regulating blood flow.
Star-shaped cells that form connections with both neurons and blood vessels, helping coordinate barrier function.
Nerve cells that communicate their metabolic needs to the vascular system.
This coordinated cellular team works together to maintain the brain's carefully balanced environment while supplying essential nutrients and oxygen to active brain regions 1 .
When the blood-brain barrier functions properly, it maintains the precise chemical environment necessary for optimal brain function. However, when it becomes compromised—"leaky"—it can contribute to numerous neurological disorders:
Alzheimer's and Parkinson's diseases involve breakdown of barrier integrity.
Blood flow disruption damages barrier function, leading to dangerous swelling.
Immune cells cross the barrier, attacking the protective covering of nerve fibers.
Recent research has also revealed the BBB's role in the gut-brain axis, suggesting that signals from our digestive system can influence barrier integrity, potentially connecting metabolic health with brain health 1 .
The very effectiveness of the blood-brain barrier creates a major challenge for treating brain diseases: approximately 98% of potential therapeutic molecules cannot cross it 1 . This has forced scientists to develop creative strategies to overcome this obstacle.
One of the most significant challenges in BBB research has been creating laboratory models that accurately mimic the human barrier. Animal models, while valuable, often don't perfectly predict human responses. Cell models grown in standard dishes typically lack the complexity of the living brain environment. A team from Chiba University in collaboration with pharmaceutical companies presented a solution to this problem at CVB 2019: a novel human immortalized cell-based BBB triple co-culture model 1 .
The researchers employed a systematic approach to create their advanced model:
They used immortalized human brain microvascular endothelial cells (HBMEC/ci18), astrocytes (HASTR/ci35), and pericytes (HPBC/ci37)—ensuring a consistent, reproducible cell source.
Unlike simpler models that use only endothelial cells, this approach cultured all three cell types together, recreating the natural cellular environment of the neurovascular unit.
The team measured several key indicators of barrier integrity:
Using qPCR and immunocytochemistry to verify that the cells expressed appropriate BBB-specific genes and proteins.
Testing how well known CNS-active and CNS-excluded compounds could cross their model barrier 1 .
The triple co-culture model demonstrated significantly enhanced barrier properties compared to standard models:
Most importantly, when testing compounds with known brain penetration characteristics, the model correctly distinguished between brain-permeating and excluded substances:
| Compound | CNS Status | Permeability (Pe × 10⁻⁶ cm/s) |
|---|---|---|
| Memantine | Positive | 522 ± 100 |
| Diphenhydramine | Positive | 1398 ± 324 |
| Propranolol | Positive | Data not specified |
| Pyrilamine | Positive | Data not specified |
| Quinidine | Negative | 161 ± 31 |
| Desloratadine | Negative | Data not specified |
| Rhodamine 123 | Negative | Data not specified |
| Lucifer Yellow | Negative | 21 ± 11 |
| Sodium Fluorescein | Negative | Data not specified |
| Data adapted from Kitamura et al. 1 | ||
The model successfully separated CNS-positive compounds (which showed high permeability) from CNS-negative compounds (which showed low permeability), validating its predictive capability for drug development applications.
Advances in blood-brain barrier research depend on specialized reagents and tools that enable scientists to create increasingly sophisticated models and experiments. Here are some key research solutions driving the field forward:
| Tool/Reagent | Function in Research | Application Examples |
|---|---|---|
| Immortalized cell lines (HBMEC/ci18, HASTR/ci35, HPBC/ci37) | Provide consistent, reproducible human cell sources for barrier models | Creating scalable, standardized BBB models for drug screening 1 |
| Transwell-like systems | Physical platforms for growing barrier models between compartments | Measuring permeability and TEER in static culture conditions 1 |
| Microelectric organ-on-a-chip devices | Miniaturized systems with integrated electrodes for TEER measurement | Real-time barrier integrity monitoring under flow conditions 2 |
| P-glycoprotein substrates (Rhodamine 123, quinidine) | Probe compounds that assess transporter activity | Evaluating efflux transporter function in BBB models 1 |
| Paracellular permeability tracers (Lucifer Yellow, sodium fluorescein) | Small fluorescent molecules that cannot cross intact barriers | Testing tight junction integrity between endothelial cells 1 |
| qPCR assays for BBB-specific genes | Measure expression of transporters, tight junctions, and receptors | Validating the molecular characteristics of BBB models 1 |
Advanced co-culture models that better mimic the in vivo neurovascular unit environment.
Microfluidic devices that simulate blood flow and mechanical forces on the BBB.
Advanced microscopy and tracer techniques to visualize barrier integrity in real-time.
The research presented at CVB 2019 points to several exciting directions for the future of cerebrovascular biology:
The development of more human-relevant models opens the possibility of patient-specific BBB models. Scientists envision using stem cell technology to create blood-brain barrier models from individual patients, which could help predict their specific responses to medications and susceptibility to neurological diseases.
The microelectric organ-on-a-chip device presented by Santa-Maria and colleagues represents the cutting edge of BBB modeling technology 2 . This reusable platform incorporates:
Emerging research highlighted at the conference suggests several promising approaches for treating BBB-related disorders:
Targeting specific transport systems to improve drug delivery to the brain.
Developing biologic therapies that can cross the barrier via receptor-mediated transport.
Stabilizing barrier function in conditions like multiple sclerosis and Alzheimer's disease.
The research presented at the 13th International Conference on Cerebral Vascular Biology represents a transformative period in our understanding of the blood-brain barrier. No longer viewed as a simple, static wall, the BBB is now recognized as a dynamic, multicellular interface that plays active roles in both brain health and disease.
The development of sophisticated laboratory models that accurately predict human brain penetration of medications marks a significant advancement toward more effective treatments for neurological and psychiatric disorders. As these models continue to improve and technologies like organs-on-chips become more widespread, we move closer to a future where drug development for brain diseases becomes faster, cheaper, and more successful.
The blood-brain barrier has long been nature's ultimate security system, protecting our most vital organ but also preventing life-saving treatments from reaching their targets. Thanks to the innovative research happening in laboratories worldwide, we are learning not to break this barrier, but to understand its language and work with its sophisticated mechanisms—potentially opening new frontiers in treating everything from brain cancer to Alzheimer's disease. The future of brain health depends on understanding this remarkable gateway, and the progress showcased at CVB 2019 suggests we're well on our way to doing just that.
This article was based on research presented at the 13th International Conference on Cerebral Vascular Biology (CVB 2019), held June 25-28, 2019 in Miami, Florida 1 .
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