Modulation of blood-brain barrier permeability by neutrophils: in vitro and in vivo studies

Shannon L. Joice, Firdaus Mydeen, Pierre Olivier Couraud, Babette B. Weksler, Ignacio A. Romero, Paul A. Fraser, Alexander S. Easton

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

74 Citas (Scopus)

Resumen

The blood-brain barrier (BBB) restricts solute permeability across healthy cerebral endothelial cells. However, during inflammation, permeability is increased and can lead to deleterious cerebral edema. Neutrophils are early cellular participants in acute inflammation, but their effect on BBB permeability is unclear. To study this, neutrophils were applied in a resting and activated state to in vitro and in vivo models of the BBB. In vitro, human neutrophils (5 × 106/ml) were activated with tumor necrosis factor (100 U/ml) and leukotriene B4 (10-7 mol/l). Untreated neutrophils reduced permeability across the human brain endothelial cell line hCMEC/D3. Activated neutrophils returned permeability to baseline, an effect blocked by the reactive oxygen scavengers superoxide dismutase (10 U/ml) and catalase (1000 U/ml). In vivo, human neutrophils (2.5 × 105 in 4 μl) were injected into the striatum of anesthetized juvenile Wistar rats, and BBB permeability measured 30 min later. This was compared to control injections (4 μl) of vehicle (0.9% saline) and arachidonic acid (10-3 mol/l). The injection generated a small hematoma around the injection tract (< 3 μl). Untreated neutrophils induced significantly lower permeability in their vicinity than activated neutrophils, with a trend to lowered permeability compared to the vehicle control. Neither untreated nor activated neutrophils induced permeability increases, while arachidonic acid increased permeability as a positive control. This study further delineates the effect of neutrophils on the BBB, and demonstrates that resting neutrophils induce acute reductions in permeability while activated neutrophils have a neutral effect. The in vivo model reiterates some aspects of acute intracerebral hemorrhage.

Idioma originalEnglish
Páginas (desde-hasta)13-23
Número de páginas11
PublicaciónBrain Research
Volumen1298
DOI
EstadoPublished - oct. 28 2009

Nota bibliográfica

Funding Information:
This work was funded by the Heart and Stroke Foundation of Canada and the Nova Scotia Health Research Foundation (grants to ASE).

ASJC Scopus Subject Areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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