Abstract
Leukocyte accumulation in cerebrospinal fluid and disruption of the blood- brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine- induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/μl as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P- and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P- and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P- and E-selectins cooperatively contribute to meningitis and that functional blocking of both endothelial selectins in conjunction with antibiotics may provide a therapeutic approach for treatment of bacterial meningitis.
Original language | English (US) |
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Pages (from-to) | 2485-2490 |
Number of pages | 6 |
Journal | Journal of Clinical Investigation |
Volume | 97 |
Issue number | 11 |
DOIs | |
State | Published - Jun 1 1996 |
Externally published | Yes |
Keywords
- blood-brain barrier
- cerebrospinal fluid
- endothelium
- inflammation
- leukocytes
ASJC Scopus subject areas
- General Medicine