memory care patient and caregiver

The Importance of BBB Models & Measurement

A Focus on Transepithelial Electrical Resistance

Adrienne L. Watson, PhD, Chief Scientific Officer, World Precision Instruments

 

IntroductionMemory care patient and caregiver

The blood-brain barrier (BBB) is a complex, specialized, and intricate system that plays a critical role in maintaining the homeostasis of the central nervous system (CNS). It acts as a protective barrier, regulating the exchange of substances between the blood and the brain. Understanding the structure, function, and measurement techniques of the BBB is of paramount importance for various fields, including neuroscience, pharmacology, and drug delivery. This article aims to explore the importance of studying the BBB, the value of BBB models and the various measurement techniques such as transepithelial electrical resistance (TEER) that aid in BBB assessment.

The Blood-Brain Barrier: An Overview

The BBB is a dynamic interface between the blood vessels and the brain, consisting of specialized endothelial cells, tight junctions, astrocytes, pericytes, and basement membrane components. It acts as a physical and biochemical barrier, preventing the free passage of most molecules and substances from the blood into the brain. This selective permeability is essential for maintaining the optimal environment for neuronal function and protecting the brain from potentially harmful substances such as pathogens and toxins. The BBB is a critical barrier to overcome in order to treat brain pathologies with therapeutics, and BBB models are crucial for the development of brain-targeting drugs.

Neurological Disorders and Diseases

Studying the BBB is central for understanding the pathogenesis and progression of various neurological disorders and diseases. Dysfunction of the BBB has been implicated in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and brain tumors. By investigating the changes in BBB integrity and permeability in these conditions, researchers can gain insights into disease mechanisms and identify potential therapeutic targets.

Drug Delivery and Therapeutics

The BBB poses a significant challenge in drug delivery to the brain. Many potentially beneficial drugs are unable to effectively cross the BBB, limiting their effectiveness in treating diseases of the CNS. Understanding the transport mechanisms and regulation of BBB permeability can aid in the development of strategies to enhance drug delivery to the brain. Techniques such as targeted drug delivery systems, nanocarriers, and temporary disruption of the BBB are being actively explored to improve drug penetration and efficacy.

Neuropharmacology and Toxicology

Studying the BBB is essential in neuropharmacology and toxicology research. The BBB acts as a gatekeeper, controlling the entry of drugs and toxins into the brain. Understanding the transporters and receptors involved in drug uptake and efflux at the BBB can help in predicting drug efficacy and potential adverse effects. Additionally, studying the BBB's response to toxins and environmental pollutants can provide insights into their neurotoxicity and aid in the development of preventive measures.

Measurement Techniques for Assessing the Blood-Brain Barrier: Transepithelial Electrical Resistance (TEER)

TEER is a widely used technique for assessing the integrity and permeability of the BBB in cell culture and microphysiological systems such as organ on chips. TEER measures the electrical resistance across a monolayer of endothelial or epithelial cells. The TEER value reflects the tightness of the tight junctions between the cells, a key determinant of BBB function. Decreased TEER values indicate increased permeability and compromised barrier integrity. TEER measurements have been taken in cell culture and organ on chip systems and these TEER values have been correlated to the permeability of the BBB to various compounds and drugs.

Other Techniques for BBB Assessment

In addition to TEER, several other techniques are used to assess the BBB in vitro and in vivo:

  1. In Vitro Models: Cell culture models, such as co-cultures of endothelial cells with astrocytes or pericytes, provide a simplified representation of the BBB. These models allow for the study of BBB transport mechanisms, drug permeability, and interactions with other cell types.
  2. In Vivo Imaging Techniques: Advanced imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), can be used to visualize and quantify BBB integrity and permeability in live animals and humans. These techniques provide valuable information about BBB dysfunction in various neurological disorders.
  3. Molecular Imaging and Biomarkers: Molecular imaging techniques, including fluorescence imaging and radiolabeling, can be used to visualize specific molecules and receptors at the BBB. Biomarkers, such as tight junction proteins and transporters, can be targeted to assess BBB integrity and function.

Clinical Implications and Future Directions

Understanding the BBB's role in neurological disorders and drug delivery has significant clinical implications. Targeted drug delivery strategies, such as using nanoparticles or receptor-mediated transport, can enhance drug efficacy while minimizing systemic side effects. Additionally, advancements in BBB research may lead to the development of novel therapeutic approaches for neurodegenerative diseases and brain tumors. The ability to accurately and non-invasively measure the BBB with TEER allows researchers and drug developers to rapidly assess hundreds or thousands of compounds for treating CNS diseases.

Future directions in BBB research include exploring the role of the BBB in neuroinflammation, neurovascular coupling, and neurodegeneration. Further understanding of the molecular mechanisms involved in BBB regulation and transport will pave the way for the development of innovative therapies and diagnostic tools. Finally, implementing BBB permeability measurements, such as TEER, across a wide variety of BBB models will enable standardized and high throughput assessment of therapeutics needed to improve the lives of patients.

Conclusion

Studying the blood-brain barrier is of utmost importance in various fields, including neuroscience, pharmacology, and drug delivery. The BBB's selective permeability and regulation of substance exchange between the blood and the brain play a crucial role in maintaining CNS homeostasis. Measurement techniques such as TEER provide valuable insights into BBB integrity and permeability. Advancements in BBB research have the potential to revolutionize drug delivery to the brain and improve the understanding and treatment of neurological disorders.

References

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