Blood-Brain Barrier

What is the blood-brain barrier?

Your blood-brain barrier (BBB) is a protective layer that lines the inner surfaces of the blood vessels inside your brain. It’s a key part of how your brain and nervous system work.

Though the name includes the word “barrier,” it’s really more of a filter and behaves like a gatekeeper to your brain. It’s there to keep harmful things out and hold helpful things in. It also controls how various chemical molecules (including compounds your body needs or makes itself) enter and exit your brain.

What does the blood-brain barrier do?

Inside your blood vessels is a layer of specialized cells called the endothelium. But inside your brain, the endothelium is different.

Endothelial cells lining the inside of your brain’s blood vessels are tightly packed together, forming your blood-brain barrier. They’re so tightly packed that there’s almost no space for anything to slip through without help. These cells have a lipid-based outer membrane.

What can get through the BBB?

Some things can get through your BBB if they’re small enough. Others can get through because they’re lipid-soluble. That means they can pass through your blood-brain barrier without it repelling them. Larger or water-soluble molecules can’t get through the BBB on their own.

Large molecules can’t slip between the interlocking endothelial cells because of their size. Water-soluble molecules can’t easily pass through your BBB because its cell membranes are lipid-based, which repels water-soluble molecules. If large or water-soluble molecules — including nutrients — need to get through, they need transportation to help them across.

Some examples of drugs and substances that can get through the BBB (either on their own or with transport help) include:

• Alcohol.
• Anesthetics.
• Antidepressant medications.
• Anxiolytics (antianxiety medications).
• Antipsychotic medications.
• Medications that treat seizures or epilepsy.
• Caffeine.
• Acetaminophen and most nonsteroidal anti-inflammatory drugs (NSAIDs).
• Sedative hypnotics (such as barbiturates, benzodiazepines and similar drugs).

The above list mainly refers broadly to medication classes that can pass through your BBB. But medications from many more classes can also make it through. The list of what can make it through your BBB is extremely lengthy, so medications that fall into the above classes make up only a fraction of the medications that can cross your BBB.

Right now, the best methods to find or predict which compounds can pass through your BBB involve highly complex algorithms and computer programming. So far, these methods list nearly 5,000 chemical molecules (including medications) that can (or should be able to) pass through your BBB.

What can’t pass through the blood-brain barrier?

Pathogens, such as bacteria or viruses, and many toxic substances generally can’t get through your BBB.

What are the common conditions and disorders that affect the blood-brain barrier?

Your blood-brain barrier is highly secure, but it isn’t perfect. Inflammation can weaken it. Other conditions can also make it less effective. That can let harmful substances or pathogens into your brain (it can also make some medications, such as penicillin-type antibiotics, more effective at treating infections in your brain).

Conditions that involve any weakening in your BBB’s integrity include both acute and chronic illnesses.

Acute conditions involving weakened BBB integrity

Acute conditions are issues that are happening right now or very recently. Examples of acute conditions that can affect your BBB include (but aren’t limited to):

• Brain cancers.
• Brain infections (encephalitis and meningitis).
• Concussion and traumatic brain injury (TBI).
• High blood carbon dioxide levels (hypercapnia).
• Low blood oxygen levels (cerebral hypoxia).
• Stroke.
• Seizures (especially ones that turn into status epilepticus).

Chronic conditions involving weakened BBB integrity

Chronic conditions are long-term concerns. They can last months (at minimum), but many — if not most — are permanent and can last for years. These include (but aren’t limited to):

• Alzheimer’s disease.
• Amyotrophic lateral sclerosis (ALS).
• Chronic hypercapnia from conditions like chronic obstructive pulmonary disease (COPD).
• Epilepsy.
• Frontotemporal dementia.
• High blood pressure (hypertension).
• High blood sugar (hyperglycemia) and related conditions like Type 2 diabetes.
• High cholesterol (hyperlipidemia).
• Multiple sclerosis.
• Neuromyelitis optica (NMO).
• Parkinson’s disease.

Experts suspect many other chronic conditions can affect your BBB, but more research is necessary to confirm this.

Common signs or symptoms of blood-brain barrier disruptions

For now, there’s no clear way to identify problems with your BBB. Some lab tests may be able to indirectly hint at BBB issues, especially tests on cerebrospinal fluid. Most conditions that involve BBB disruptions become apparent through symptoms that aren’t related to your barrier.

Experts are working on ways to weaken the BBB temporarily using magnetic resonance imaging-guided focused ultrasound. That may allow molecules inside of your brain to escape into your blood, making them easier to detect. Those molecules might be the key to detecting and diagnosing conditions like brain cancer, Alzheimer’s disease and Parkinson’s disease earlier. It might also allow some medications to make it through and treat conditions like cancer inside the brain. However, this research is still in its early stages, and it will take more research to determine if this is possible.

Are there any common treatments that target the blood-brain barrier?

For now, there aren’t any treatments that target your blood-brain barrier directly. Instead, treatments target conditions that could disrupt your BBB. Some examples include:

• Medications for high blood pressure, high cholesterol or high blood sugar.
• Treatments to restore blood circulation in your brain after an ischemic stroke (this is a stroke that involves a blockage that cuts off blood flow to part of your brain).
• Medications that prevent seizures.
• Treatments for brain cancer.

What can I do to take care of the health of my blood-brain barrier?

There’s no direct way to prevent disruptions that affect your BBB. Instead, the best approach is to avoid conditions or circumstances that could lead to its disruption. Some things you can do include:

• Eat a balanced diet and maintain a healthy weight. Conditions affecting circulatory health, especially stroke, can disrupt your blood-brain barrier. Reaching and maintaining a weight that’s healthy for you and following dietary guidance from your primary care provider are very important. They can help you prevent — or at least delay or reduce the severity of — a stroke. That can help protect your BBB.
• Don’t ignore infections. Eye and ear infections can spread and cause inflammation that disrupts your BBB. That can let them access your brain, which can be serious or deadly.
• Wear safety equipment. Head injuries can cause disruptions in your BBB. Using safety equipment — especially helmets and seat belts (or other vehicle safety restraints) — can help you avoid head injuries that could disrupt your blood-brain barrier.
• Manage your health conditions. Chronic conditions like Type 2 diabetes, high blood pressure, high cholesterol and epilepsy can disrupt your BBB and the blood vessels it surrounds. Managing these conditions, with either medication or other treatments, is an important step in protecting your blood-brain barrier.

How do healthcare providers use what they know about the blood-brain barrier to treat medical conditions inside and outside the brain?

Your BBB is a key consideration in treating many conditions in your brain and throughout your body. That’s because many treatments — especially medications — can indirectly affect your brain if they can get through your BBB.

Other times, healthcare providers have to try to work around your BBB. That’s because it’s sometimes too good at its job. Medications that could treat infections or cancers in your brain may not be able to make it through your BBB.

To get around that, experts use medications specially formulated to avoid your blood-brain barrier’s filtering. They can use a “Trojan horse” approach, piggybacking medications on immune cells or other molecules that can get through your BBB.

Experts can also use your body’s natural chemistry to get around your BBB. An example of this is using the drug levodopa to treat Parkinson’s disease. Parkinson’s happens when there isn’t enough dopamine in your brain, which certain brain areas need for controlling muscle movements. Dopamine can’t get through your BBB, but levodopa can. Once it’s inside your brain, levodopa converts into dopamine, helping treat Parkinson’s symptoms.

Who discovered the blood-brain barrier, and how is it detectable when it’s so small?

Most sources credit other scientists, particularly Paul Ehrlich or Max Lewandowsky, with discovering the barrier in the late 1800s and early 1900s. However, the first use of the term “blood-brain barrier” was in a 1921 research paper authored by Lina Shtern (sometimes, spelled “Stern”) of Russia (in what is now Latvia) and Swiss physician Raymond Gautier.

Electron microscope images first captured in the 1960s and 1970s confirmed Shtern and Gautier’s work. Those images detailed the structure of the BBB in animal and human brains.

A note from Cleveland Clinic

Your blood-brain barrier (BBB) is a filtering layer of cells surrounding blood vessels in most areas of your brain. It’s a critical line of defense, keeping most harmful things out and most helpful things in. But it isn’t perfect. Many conditions can affect it, and healthcare providers have to consider the BBB when trying to treat all conditions, not just those that affect your brain.

While experts know much about the BBB, more research is necessary to understand all of how it works. Unlocking its inner workings can open the door to effective treatments for many brain-related conditions. That way, your BBB can become a barrier only to things that can harm you and not obstruct treatments that can help.