What Is Blood Brain Barrier And Why It Hinders Treatment?

Just like fortresses are built to protect something precious. In our bodies, this fortress is the blood-brain barrier (BBB), guarding the brain from harmful things in the blood. It's like a gatekeeper deciding who gets in and who doesn't. While its job is important, it makes treating brain problems hard.

The BBB is like a strict guard, not letting many helpful medicines through to the brain. This creates a challenge for scientists trying to find ways to treat brain diseases. They're working hard to figure out how to trick the BBB so they can deliver medicine to the brain. In this article, we'll explore what the BBB does, why it's important, and how scientists are trying to beat it to help people with brain problems.

Blood Brain Barrier

The brain is a precious organ, and over the course of evolution, it has been shielded from harm by various protective mechanisms. One obvious safeguard is our skull, which is about 7mm thick. Additionally, the brain is enveloped in protective fluid called cerebrospinal fluid and a membrane called the meninges, which further shield it from physical injury.

Another crucial defense is the blood-brain barrier, which acts as a shield between the brain's blood vessels and the cells and other components of brain tissue. While the skull, meninges, and cerebrospinal fluid protect against physical damage, the blood-brain barrier guards against harmful pathogens and toxins that might be present in the bloodstream.

Discovery of BBB

The blood-brain barrier was first discovered in the late 19th century when the German physician Paul Ehrlich injected a dye into a mouse's bloodstream. He observed that the dye spread to all tissues except the brain and spinal cord, revealing the existence of a barrier between the brain and blood. However, it wasn't until the 1960s that researchers had access to powerful enough microscopes to study the physical structure of the blood-brain barrier.

Structure of BBB

We now understand that the primary structure responsible for the blood-brain barrier's protective function is the "endothelial tight junction." Endothelial cells, which line the interior of all blood vessels, are closely packed together in the capillaries that form the blood-brain barrier, creating these tight junctions.

These tight junctions only allow small molecules, fat-soluble molecules, and some gasses to pass freely through the capillary wall and into the brain tissue. Larger molecules, like glucose, can enter through specialized transporter proteins that act as selective "doors" for specific molecules.

In addition to the endothelial cells, other components surrounding the blood vessel contribute to the blood-brain barrier's function by regulating its selectivity. These components work in tandem with the endothelial cells to maintain the barrier's effectiveness in protecting the brain.

Why is the blood-brain barrier essential?

The blood-brain barrier serves a crucial role in safeguarding the brain from harmful substances like toxins and pathogens, which could otherwise lead to infections. Simultaneously, it allows essential nutrients to pass through to the brain.

Additionally, the blood-brain barrier helps maintain stable levels of hormones, nutrients, and water within the brain. Any significant fluctuations in these levels could disrupt the delicate balance necessary for optimal brain function.

What happens if the blood-brain barrier is compromised?

When the blood-brain barrier is compromised, it can lead to severe consequences. For instance, bacterial infections like meningococcal disease can cause the barrier to become more permeable. This increased permeability allows bacteria and toxins to penetrate brain tissue, leading to inflammation and, in some cases, fatalities.

In certain conditions such as multiple sclerosis, the blood-brain barrier's functionality is impaired. This impairment results in white blood cells infiltrating the brain and attacking the neurons' ability to communicate effectively. As a consequence, the signaling between neurons becomes disrupted, leading to various neurological problems.

Which Substances Can Pass Through the Blood Brain Barrier?

Certain substances can permeate the blood-brain barrier due to their size or chemical properties. Small molecules and lipid-soluble substances can cross the BBB more easily, while larger or water-soluble molecules face barriers.

Large molecules are hindered by the tight junctions between endothelial cells, which prevent them from passing through. Water-soluble molecules struggle to cross because the BBB's cell membranes repel them. In cases where large or water-soluble molecules, like nutrients or medications, need to traverse the BBB, they require assistance for transport.

Various drugs and compounds can pass through the BBB, either independently or with assistance. These include alcohol, anesthetics, antidepressants, anxiolytics, antipsychotics, medications for seizures or epilepsy, caffeine, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and sedative-hypnotics like barbiturates and benzodiazepines. However, this list only covers some broad categories, and many more medications can cross the BBB.

Identifying which compounds can penetrate the BBB relies on complex algorithms and computer programs. Currently, these methods have identified nearly 5,000 chemical molecules, including medications, which can or should be able to traverse the BBB.

Why does BBB hinder Treatment?

The Blood-Brain Barrier (BBB) serves as a formidable defense mechanism shielding the brain from potentially harmful substances circulating in the bloodstream. Its primary function is to maintain the delicate neural environment by regulating the passage of molecules into and out of the brain. While this protective barrier is crucial for preventing neurotoxicity and maintaining brain homeostasis, it poses significant challenges for the delivery of therapeutic agents intended to treat various neurological disorders.

The BBB's formidable nature arises from several key factors:

Tight Junctions

The BBB's endothelial cells are interconnected by specialized structures known as tight junctions, which form a selective barrier that controls the movement of molecules between the blood and the brain. While essential nutrients like glucose and oxygen can pass through these junctions, larger molecules and potentially harmful substances are effectively restricted.

Efflux Pumps

In addition to tight junctions, efflux pumps located on the surface of endothelial cells actively pump out foreign substances that manage to breach the barrier. This efflux mechanism further limits the penetration of therapeutic drugs into the brain, reducing their effectiveness.

Molecular Size

The size and complexity of molecules play a crucial role in their ability to traverse the BBB. Larger and more complex molecules, often characteristic of effective therapeutic agents for neurological conditions, face greater challenges in crossing this barrier.

The dual nature of the BBB as both a protective shield and a formidable obstacle underscores its significance in neurological health and disease. While its protective role is essential for maintaining brain function, its restrictive nature poses a significant challenge for the development of treatments targeting neurological disorders such as Alzheimer's disease, Parkinson's disease, and brain tumors.

Latest research on overcoming the therapeutic hindrance of BBB

Current research efforts aimed at overcoming the BBB's limitations are focused on innovative strategies, including:

Nanocarriers

Utilizing nanoparticles such as liposomes to encapsulate therapeutic agents, allowing them to bypass the BBB and reach their target sites within the brain. 

Antibody-Drug Conjugates

Combining therapeutic molecules with antibodies that can selectively bind to receptors on BBB endothelial cells, facilitating targeted delivery of drugs into the brain.

Disruption of the Barrier

Investigating methods to temporarily and selectively disrupt the BBB at specific sites, enabling enhanced penetration of therapeutic agents into the brain.

While these strategies hold promise for overcoming the challenges posed by the BBB, further research is needed to develop safe and effective approaches for delivering therapeutic agents to the brain. As our understanding of the BBB continues to evolve, it is hoped that these advancements will lead to improved treatments for neurological disorders, ushering in a new era of neurological care that harnesses the brain's protective mechanisms for therapeutic benefit.

Final Words

The Blood-Brain Barrier (BBB) is essential for preventing neurotoxicity, but it poses challenges for delivering therapeutic drugs to treat neurological disorders due to its selective permeability and efflux mechanisms. Strategies such as nanocarriers, antibody-drug conjugates, and disrupting the barrier are being explored to overcome these challenges. These advancements offer hope for improved treatments for conditions like Alzheimer's and Parkinson's disease by leveraging the BBB's protective mechanisms for therapeutic benefit.