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

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

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 x 10(6)/ml) were activated with tumor necrosis factor (100 U/ml) and leukotriene B-4 (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 x 10(5) in 4 mu l) were injected into the striatum of anesthetized juvenile Wistar rats, and BBB permeability measured 30 min later. This was compared to control injections (4 mu l) of vehicle (0.9% saline) and arachidonic acid (10(-3) mol/l). The injection generated a small hematoma around the injection tract (
Original languageEnglish
Pages (from-to)13 - 23
Number of pages11
JournalBrain Research
Volume1298
DOIs
Publication statusPublished - 28 Oct 2009

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