Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat.

Abstract

SummaryInjury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was : (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex ; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis . These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention .

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

“…In bacterial meningitis, the blood-CSF/blood-brain barrier is becoming leaky by the opening of intercellular tight junctions of the vessel walls particularly within venules (197). Moreover, the CSF outflow resistance increases, leading to a moderate reduction of the CSF production and absorption rates (216), and the activity of P-gp can be inhibited by proinflammatory cytokines (254).…”

Leptin Resistance and Obesity

“…1) [42,43]. However, the exact mechanism of leptin transport into the brain has not yet been clarified.…”

Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways

“…Capillary endothelial cells are (a) a major cellular substrate of the BBB; (b) a potential site of entry for bacteria into the brain (2); (c) a source of inflammatory mediators (3); (d) participants in the inflammatory recruitment of leukocytes (3,4); and (e) a critical part of the neural stem cell niche (5). The BBB is functionally (6) and structurally (7) injured in meningitis and in encephalopathy as a manifestation of sepsis in the brain (8).…”