CHEMICAL COMPOSITION OF BLOOD-BRAIN BARRIER

 

BBB Breakdown Causes

The blood-brain barrier (BBB) is a protective barrier that separates the blood circulating in the body from the brain tissue. Its primary function is to regulate the passage of substances between the bloodstream and the brain to maintain a stable and controlled environment for the brain. However, in certain situations, the BBB can become compromised or “broken,” allowing substances to cross into the brain tissue in an unregulated manner. This breakdown of the BBB can occur due to various factors and mechanisms, including:

1. Physical Injury: Traumatic brain injuries, such as a severe blow to the head, can disrupt the integrity of the BBB by damaging blood vessels and the surrounding tissues.
2. Infection and Inflammation: Infections of the central nervous system, such as meningitis, or inflammatory conditions like multiple sclerosis, can trigger an immune response that compromises the BBB’s integrity.
3. Disease: Some medical conditions, such as brain tumors and certain neurodegenerative diseases, can weaken the BBB or cause localized breaches.
4. Medications and Toxins: Certain drugs, toxins, or chemicals may have the ability to cross the BBB and damage its structural integrity, leading to a breach.
5. Hypertension: High blood pressure can strain blood vessels in the brain, potentially causing damage to the BBB over time.
6. Age: Aging can lead to changes in the BBB’s function and integrity, making it more susceptible to breakdown.

When the BBB is compromised, it can allow harmful substances, pathogens, or immune cells to enter the brain, which can result in inflammation, neural damage, and various neurological symptoms. The extent of the BBB break can vary from minor disruptions to severe breaches, depending on the underlying cause and the affected region of the brain. Treatment for BBB disruption typically focuses on addressing the underlying cause and managing the associated neurological symptoms.

 

Diseases effecting blood-brain barrier

The blood-brain barrier (BBB) is a highly selective semipermeable membrane that separates the bloodstream from the brain’s extracellular fluid. Several diseases and conditions can affect the BBB, compromising its integrity and function. Here are some diseases and details on how they impact the BBB:

1. Multiple Sclerosis (MS):
   • MS is an autoimmune disease where the immune system mistakenly attacks the protective myelin sheath covering nerve fibers.
   • Inflammation in MS can disrupt the BBB, allowing immune cells and molecules to enter the brain, leading to further damage.
2. Alzheimer’s Disease:
   • Alzheimer’s is a neurodegenerative disease characterized by the accumulation of beta-amyloid plaques in the brain.
   • These plaques can damage BBB integrity, making it more permeable and allowing harmful substances to enter the brain.
3. Stroke:
   • A stroke can cause damage to blood vessels in the brain, leading to BBB disruption.
   • This disruption can result in the leakage of blood components and inflammation, exacerbating brain injury.
4. Traumatic Brain Injury (TBI):
   • A severe blow to the head can damage blood vessels, leading to BBB breakdown.
   • This disruption can contribute to the inflammation and swelling seen in TBI.
5. Infections:
   • Infections like meningitis and encephalitis can directly affect the BBB.
   • Pathogens can breach the barrier, causing inflammation and potentially leading to neurological complications.
6. Brain Tumors:
   • Brain tumors can exert pressure on nearby blood vessels, compromising BBB integrity.
   • Additionally, tumor cells may release factors that disrupt the BBB, allowing tumor cells to infiltrate the brain.
7. Epilepsy:
   • Recurrent seizures in epilepsy can lead to chronic inflammation in the brain.
   • This inflammation can impact the BBB and make it more permeable, potentially contributing to the progression of epilepsy.
8. Autoimmune Encephalitis:
   • Autoimmune encephalitis is characterized by the immune system mistakenly attacking brain tissue.
   • This autoimmune response can disrupt the BBB, leading to neurological symptoms.
9. Hypertension:
   • Chronic high blood pressure can damage blood vessels throughout the body, including those in the brain.
   • BBB disruption due to hypertension can contribute to cognitive impairment.
10. Substance Abuse:
    • Certain drugs of abuse, such as methamphetamine, can directly impact BBB function.
    • Prolonged substance abuse can lead to BBB leakage and brain damage.

Understanding how these diseases affect the blood-brain barrier is crucial for developing treatments and interventions to mitigate the damage and improve patient outcomes.

 

Brain-Targeting Drugs

There are many drugs that target the brain for various medical purposes. Here is a list of some of them, categorized by their primary use:

1. Pain Relief and Analgesics:
   • Acetaminophen
   • Ibuprofen
   • Morphine
   • Oxycodone
2. Antidepressants:
   • Selective Serotonin Reuptake Inhibitors (SSRIs) like Prozac, Zoloft
   • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) like Cymbalta, Effexor
   • Tricyclic Antidepressants (TCAs) like Amitriptyline, Imipramine
3. Antipsychotics:
   • Haloperidol
   • Risperidone
   • Aripiprazole
4. Anti-Anxiety Medications:
   • Benzodiazepines like Diazepam (Valium), Alprazolam (Xanax)
   • Buspirone
5. Anti-Epileptic Drugs:
   • Phenobarbital
   • Valproic Acid
   • Levetiracetam
6. Stimulants (for ADHD):
   • Methylphenidate (Ritalin)
   • Amphetamine-Dextroamphetamine (Adderall)
7. Sedatives and Hypnotics (for sleep disorders):
   • Zolpidem (Ambien)
   • Eszopiclone (Lunesta)
8. Cognitive Enhancers (for conditions like Alzheimer’s disease):
   • Donepezil (Aricept)
   • Memantine (Namenda)
9. Mood Stabilizers (for bipolar disorder):
   • Lithium
   • Lamotrigine (Lamictal)
10. Nootropics (cognitive enhancers):
    • Modafinil
    • Piracetam
11. Opioid Analgesics (for severe pain):
    • Fentanyl
    • Hydrocodone
12. Anti-Parkinson’s Drugs:
    • Levodopa/Carbidopa (Sinemet)
    • Pramipexole (Mirapex)
13. Cholinesterase Inhibitors (for Alzheimer’s disease):
    • Rivastigmine (Exelon)

Please note that these drugs should only be used under the guidance and prescription of a qualified healthcare professional. They may have side effects and interactions with other medications, and their use should be carefully monitored.

 

Drug delivery across the blood-brain barrier

Drug delivery across the blood-brain barrier (BBB) is a complex and highly regulated process due to the BBB’s unique structure, which is designed to protect the brain from harmful substances while allowing essential nutrients to pass through. Here’s a detailed description of how drug delivery across the BBB works:

1. Blood-Brain Barrier Structure:
   • The BBB is composed of specialized brain capillary endothelial cells that are tightly interconnected by tight junctions. These junctions prevent the free diffusion of most substances from the bloodstream into the brain.
2. Passive Diffusion:
   • Small lipophilic (fat-soluble) molecules can passively diffuse through the lipid bilayer of endothelial cells. This includes some gases like oxygen and carbon dioxide and small lipophilic drugs. However, most therapeutic molecules are too large or hydrophilic to passively diffuse.
3. Transport Proteins:
   • The BBB is equipped with various transport proteins that facilitate the selective transport of specific molecules. For example:
     • Glucose Transporters: Glucose is essential for brain function, and GLUT1 transporters mediate its transport into the brain.
     • Amino Acid Transporters: Amino acids required for protein synthesis are transported by specific carriers.
     • Efflux Transporters: ATP-binding cassette (ABC) transporters, such as P-glycoprotein, actively pump out drugs and toxins from the brain to the bloodstream, limiting drug access.
4. Receptor-Mediated Transport:
   • Some molecules can bind to specific receptors on the surface of endothelial cells, triggering receptor-mediated transport mechanisms. For example, transferrin receptors can transport iron-bound drugs.
5. Carrier-Mediated Transport:
   • Specialized carrier proteins transport various nutrients and drugs across the BBB. These carriers are selective and ensure that only necessary substances are transported. Examples include the large neutral amino acid transporter (LAT1) for certain amino acids and organic anion transporters (OATs).
6. Nanoparticle-Based Drug Delivery:
   • Nanoparticles, such as liposomes or polymeric nanoparticles, can be engineered to encapsulate drugs. These nanoparticles can sometimes bypass the BBB’s defenses and release drugs at the desired site within the brain.
7. Intranasal Delivery:
   • Some drugs can be delivered directly to the brain via the olfactory or trigeminal nerves by intranasal administration. This method can bypass the BBB to some extent.
8. Focused Ultrasound and Microbubbles:
   • Non-invasive techniques like focused ultrasound, in combination with microbubbles, can temporarily disrupt the BBB, allowing drugs to pass through. This is still an area of active research.
9. Chemical Modifiers:
   • Researchers are exploring various chemical modifiers, such as prodrugs or peptide shuttles, to enhance the transport of drugs across the BBB.
10. Targeted Drug Delivery:
    • Advancements in molecular biology and nanotechnology enable the design of drugs with specific receptors or ligands that can target BBB transporters, increasing drug delivery efficiency.

It’s essential to note that drug delivery to the brain remains a significant challenge, and the choice of delivery method depends on the drug’s properties, the disease being treated, and the desired therapeutic outcome. Researchers continue to explore innovative strategies to improve drug delivery across the BBB for neurological conditions like Alzheimer’s disease, Parkinson’s disease, and brain tumors.