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The quantitative relationship between the disruption of the blood-brain barrier (BBB) and the recruitment of glial cells was explored in a mouse model of endotoxemia. 18 F2-Fluoro-2-deoxy-sorbitol ( 18 FFDS) PET imaging was used as a paracellular marker for quantitative monitoring of BBB permeability after i.v injection of increasing doses of lipopolysaccharide (LPS) or vehicle (saline, n = 5). The brain distribution of 18 FFDS ( V T , mL.cm −3 ) was estimated using kinetic modeling. LPS dose-dependently increased the brain V T of 18 FFDS after injection of LPS 4 mg/kg (5.2 ± 2.4-fold, n = 4, p 0.05, n = 7). In 12 individuals belonging to the different groups, changes in BBB permeability were compared with expression of markers of astrocyte (GFAP) and microglial cell (CD11b) using ex vivo immunohistochemistry. Increased expression of CD11b and GFAP expression was observed in mice injected with 3 mg/kg of LPS, which did not increase with higher LPS doses. Quantitative 18 FFDS PET imaging can capture different levels of BBB permeability in vivo. A biphasic effect was observed with the lowest dose of LPS that triggered neuroinflammation without disruptive changes in BBB permeability, and higher LPS doses that increased BBB permeability without additional recruitment of glial cells.
Leterrier et al. (Tue,) studied this question.