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Environ Toxicol Pharmacol. 1998 Jan;5(1):35-41.

Roles of nitric oxide and prostaglandins in the increased permeability of the blood-brain barrier caused by lipopolysaccharide.

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1
Laboratory of Cell Biology, Department of Anatomy, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634, Japan.

Abstract

We investigated the involvement of nitric oxide (NO) and prostaglandins (PGs) in the damage to the blood-brain barrier (BBB) induced by lipopolysaccharide (LPS), using fluorescein as a tracer in mice. Aminoguanidine, a competitive inhibitor of inducible NO synthase (iNOS), when administered s.c. at 5 mg/kg, but not 500 mg/kg, reduced significantly the increase in brain fluorescein level after its i.v. injection in LPS-treated mice. When 1000 mg/kg of l-arginine, a substrate of NOS, were co-administered with 5 mg/kg of aminoguanidine to LPS-treated mice, the inhibitory effect of aminoguanidine on the increased fluorescein level disappeared. N(G)-Nitro-l-arginine methyl ester (l-NAME), a non-isoenzyme-selective NOS inhibitor, when administered s.c. at 5 mg/kg, only slightly reduced the LPS-induced increase in the brain fluorescein level. A pretreatment with dexamethasone, which suppressed the induction of both iNOS and cyclooxygenase 2 (COX-2), tended to decrease the brain fluorescein level in LPS-treated mice. Indomethacin, a COX inhibitor, at 5 mg/kg, but not 10 mg/kg, suppressed significantly the LPS-induced increase in the brain fluorescein level. These results involve that both the NO produced by iNOS and the PGs produced by COX contribute to enhance BBB permeability in LPS-administered mice.

PMID:
21781848

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