The blood–brain-barrier in multiple sclerosis: Functional roles and therapeutic targeting

  title={The blood–brain-barrier in multiple sclerosis: Functional roles and therapeutic targeting},
  author={Jorge Correale and Andr{\'e}s Mar{\'i}a Villa},
  pages={148 - 160}
In most regions of the central nervous system (CNS), the composition of the neuronal microenvironment is maintained by virtue of particular blood–brain-barrier (BBB) characteristics, to which vascular endothelial cells (ECs) contribute an important role. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS, characterized at tissue level by multifocal perivascular infiltrates, predominantly of lymphocytes and macrophages. Thus, lymphocyte recruitment into the brain across… 

Inflammatory cell trafficking across the blood–brain barrier: chemokine regulation and in vitro models

Current knowledge of BBB cellular components, the multistep process of inflammatory cells crossing the BBB, functions of CNS‐derived chemokines, and in vitro BBB models for transmigration are summarized, with a particular focus on new and recent findings.

Neurobiology of Disease

The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms are described.

Factors controlling permeability of the blood–brain barrier

A better understanding of the factors controlling BBB permeability helps develop novel pharmacological interventions of BBB hyperpermeability under pathological conditions.

Blood–brain barrier and neurological diseases

Current knowledge of BBB cellular components and the multistep process of inflammatory cells crossing the BBB in physiological conditions are introduced, and their biological mechanisms to cross theBBB in pathological conditions in representative neurological autoimmune diseases are summarized.

Neurovascular Unit: a Focus on Pericytes

The neurovascular unit composition and the interplay between the diverse components, addressing pericytes with a particular detail are reviewed, addressing this cells with a great potential for therapy.

Structure and function of the blood–brain barrier

The Blood–Brain Barrier in Neuroinflammation

An update of the biology of the cell comprising the blood–brain barrier is described, and the pathology and pathomechanisms of BBB breakdown in neuroinflammatory diseases are highlighted.

The blood–brain barrier in health and disease

This review discusses the cellular and molecular composition of the blood–brain barrier and how the development and function of the BBB is regulated by interactions with the CNS microenvironment.

A Role for Neutrophil Recruitment? Blood-Brain Barrier Integrity through TNF: Central Nervous System Infiltration and Meningeal Mast Cells Affect Early T Cell

It is demonstrated that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry and proposed that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell in flux and myelin damage.



Delivery of therapeutic agents to the central nervous system: the problems and the possibilities.

  • D. Begley
  • Biology
    Pharmacology & therapeutics
  • 2004

Neural Induction of the Blood–Brain Barrier: Still an Enigma

This review tries to elucidate the question concerning the nature of the inductive signal eliciting blood–brain barrier formation in the cerebral microvasculature.

Statins reduce human blood–brain barrier permeability and restrict leukocyte migration: Relevance to multiple sclerosis

Evidence for the anti‐inflammatory effects of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors within the central nervous system arose from studies demonstrating that statins improve clinical signs in the animal model of MS and reduce the number of gadolinium‐enhancing lesions in MS.

Perivascular T Cells Express the Pro‐Inflammatory Chemokine RANTES mRNA in Multiple Sclerosis Lesions

Results imply that RANTES in MS lesions may play an important role in the activation and/or selective accumulation of memory T cells and, thereby, in the pathogenic events associated with MS.

Basement Membrane Proteins in Multiple Sclerosis-Associated Inflammatory Cuffs: Potential Role in Influx and Transport of Leukocytes

It is postulated that BM proteins within inflammatory cuffs may serve as a conduit network and therefore facilitate the transport of myelin-containing phagocytes out of the CNS toward peripheral lymph nodes.

The role of integrins in immune-mediated diseases of the nervous system

Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes.

CNS-specific N51/KC expression produced remarkable neutrophil infiltration into perivascular, meningeal, and parenchymal sites, demonstrating that this chemokine exerts the multiple functions in vivo required to recruit leukocytes into the CNS.

Induction of various blood‐brain barrier properties in non‐neural endothelial cells by close apposition to co‐cultured astrocytes

The results obtained with this heterologous co‐culture system indicate that through contact with their feet, astrocytes are capable of transdifferentiating non‐neural EC into the brain type, endowing them with the BBB properties.

Astrocytes induce blood–brain barrier properties in endothelial cells

Direct evidence is provided that astrocytes are capable of inducing blood–brain barrier properties in non-neural endothelial cells in vivo.