Vandenbroucke team - Barriers in inflammation

Research field: Gut and brain barriers in inflammatory diseases

Team leader: Prof. Dr. Roos Vandenbroucke

Tel:+32 9 33 13766 - Fax: +32 9 221 76 73
Email:Roosmarijn.Vandenbroucke.spam.detractor@irc.vib-UGentspam.corruptor.be

Research topic

Tight barriers form the major protection for the brain against external insults such as toxins, infectious agents and peripheral blood fluctuations. These barriers are a central part of the brain homeostasis mechanism and assure a balanced and well-controlled micro-environment around synapses and axons in the central nervous system (CNS). Although largely understudied, the choroid plexus epithelium (CPE), forming the blood-CSF barrier (BCSFB), is an important and unique single layer of epithelial cells situated at the interface between blood and cerebrospinal fluid (CSF) (Figure). Subtle changes in the CPE, via changes in the CSF composition, have wide-ranging effects on the brain and will subsequently affect disease progression. Therefore, understanding BCSFB functionality under physiological and pathophysiological conditions might open up new therapeutic strategies to treat inflammatory diseases.

Our research focuses on the effect of systemic inflammation (including sepsis/SIRS or other inflammatory stimuli such as (inflamm)aging) and neuroinflammation (such as the age-related disease Alzheimer’s) on the BCSFB.

We currently have different research lines:

(1) We study the key molecules that play a role in the activated detrimental processes at the BCSFB upon inflammation, focusing on barrier integrity, extracellular vesicles (exosomes), and acute phase response.

(2) We study whether the choroid plexus is ‘the missing link’ in the body-to-brain axis, due to its unique position between blood and brain. Hereto, we are investigating whether peripheral inflammatory triggers, e.g. in the gastrointestinal system, affect the CPE and consequently increase the sensitivity for the development of neuroinflammatory diseases.

(3) We explore whether the CPE can be used as a delivery route to the brain.

Area of expertise

  • Gastro-intestinal barrier
  • Sepsis and systemic inflammatory response syndrome (SIRS)
  • Aging and age-related diseases including Alzheimer’s disease
  • Extracellular vesicles and exosomes
  • Blood-brain (BBB) and blood-cerebrospinal fluid (BCSFB) barrier
  • Matrix metalloproteinases
  • Cytokine signaling

Technology transfer potential

  • Identification of novel targets or strategies to treat inflammatory diseases linked to CNS barrier dysfunction
  • Development of novel delivery strategies to target the brain

Click on the image to enlarge.

The choroid plexus protrudes in the brain ventricles, contains a single layer of tightly connected choroid plexus epithelial (CPE) cell, is responsible for most cerebrospinal fluid (CSF) production and forms a unique interface between blood and brain.

Selected publications

  1. Vandenbroucke RE et al. MMP8-dependent ECM cleavage at the blood-CSF barrier reduces survival during systemic inflammatory diseases.
    Journal of Neuroscience. 2012. Jul 18;32(29):9805-16.
  2. Vandenbroucke RE, Libert C. New hope for therapeutic matrix metalloproteinase inhibition?
    Nature Reviews Drug Discovery. 2014. Dec;13(12):904-27
  3. Van Hauwermeiren F*, Vandenbroucke RE*, et al.  TNFR1-induced lethal inflammation is mediated by goblet and Paneth cell dysfunction.
    Mucosal Immunology. 2015 Jul;8(4):828-40. *equal contribution
  4. Demeestere D et al. Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders.
    Drug Discovery Today. 2015 Aug;20(8):928-41.
  5. Brkic M et al. Amyloid β oligomers disrupt blood-cerebrospinal fluid barrier integrity by activating matrix metalloproteinases.
    Journal of Neuroscience. 2015 Sep 16;35(37):12766-78.

For publications with IRC as the affiliation, click here. For all publications, click here.

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