Subtitle: Barriers in inflammation

Vandenbroucke lab - Barriers in inflammation

Research field: Gut and brain barriers in inflammatory diseases

Group leader: Prof. Dr. Roos Vandenbroucke

Tel:+32 9 33 13730 - Fax: +32 9 221 76 73

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
  • Gut-brain axis

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

Selected publications

  1. Steeland S. et al. Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease
    EMBO Molecular Medicine, 10, e8300. 2018.
  2. Gorlé N. et al. The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection
    Brain behavior and Immunity, 69, 35-47, 2018.
  3. Balusu S. et al. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles
    EMBO Molecular Medicine, 8, 1162-1183, 2016.
  4. Brkic M et al. Amyloid beta Oligomers Disrupt Blood-CSF Barrier Integrity by Activating Matrix Metalloproteinases
    Journal of Neuroscience, 35, 12766-78, 2015.
  5. Vandenbroucke RE, Libert C. Is there new hope for therapeutic matrix metalloproteinase inhibition?
    Nature Reviews Drug Discovery, 13, 904-27, 2014.

VIB Grand Challenges Program

This research is part of the VIB Grand Challenges Program. More information, click here.

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