The blood-brain barrier significantly limits eflornithine entry into Trypanosoma brucei brucei infected mouse brain

Rodgers, J. (2008) The blood-brain barrier significantly limits eflornithine entry into Trypanosoma brucei brucei infected mouse brain. Journal of Neurochemistry, 107(4), pp. 1136-1146. (doi:10.1111/j.1471-4159.2008.05706.x)

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Abstract

Drugs to treat African trypanosomiasis are toxic, expensive and subject to parasite resistance. New drugs are urgently being sought. Although the existing drug, eflornithine, is assumed to reach the brain in high concentrations, little is known about how it crosses the healthy and infected blood–brain barrier. This information is essential for the design of drug combinations and new drugs. This study used novel combinations of animal models to address these omissions. Eflornithine crossed the healthy blood–CNS interfaces poorly, but this could be improved by co-administering suramin, but not nifurtimox, pentamidine or melarsoprol. Work using a murine model of sleeping sickness demonstrated that Trypanosoma brucei brucei crossed the blood–CNS interfaces, which remained functional, early in the course of infection. Concentrations of brain parasites increased during the infection and this resulted in detectable blood–brain barrier, but not choroid plexus, dysfunction at day 28 post-infection with resultant increases in eflornithine brain delivery. Barrier integrity was never restored and the animals died at day 37.9 ± 1.2. This study indicates why an intensive treatment regimen of eflornithine is required (poor blood–brain barrier penetration) and suggests a possible remedy (combining eflornithine with suramin). The blood–brain barrier retains functionality until a late, possibly terminal stage, of trypanosoma infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rodgers, Dr Jean
Authors: Rodgers, J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neurochemistry
ISSN:0022-3042
Published Online:24 September 2008

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