The role of the polyamine inhibitor ef lornithine in the neuropathogenesis of experimental murine African trypanosomiasis

Jennings, F. W., Gichuki, C. W., Kennedy, P. G. E., Rodgers, J. , Hunter, C. A., Murray, M. and Burke, J. M. (1997) The role of the polyamine inhibitor ef lornithine in the neuropathogenesis of experimental murine African trypanosomiasis. Neuropathology and Applied Neurobiology, 23(3), pp. 225-234. (doi:10.1111/j.1365-2990.1997.tb01206.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2990.1997.tb01206.x

Abstract

The treatment of late-stage human African trypanosomiasis is complicated by a post-treatment reactive encephalopathy, also referred to as a ‘reactive arsenical encephalopathy’, that may be fatal. This study used a well established experimental mouse system to assess the use of the trypanostatic drug, eflornithine, in the management of this post-treatment reaction. Female CD-1 mice infected with an eflornithine-resistant trypanosome stabilate and treated with the trypanocidal compound diminazene aceturate on or after day 21 post-infection develop a reactive encephalopathy and relapsing parasitaemia. If these animals are re-treated with diminazene aceturate, a severe encephalopathy develops histologically comparable with that of human cases and characterized by a severe meningoencephalitis and astrogliosis. Histopathological and immunocytochemical examination shows that administration of eflornithine before or after the development of this reactive encephalopathy prevented or ameliorated the inflammatory reaction. Since an eflornithine resistant stabilate was used, this effect appears to be independent of the drug's trypanostatic action and illustrates an important, previously unrecognized, pharmacological property of eflornithine. Consideration can now be given to the use of eflornithine for the management of human trypanosomiasis cases, even where trypanosome resistance to eflornithine exists.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Peter and Murray, Professor Maxwell and Burke, Dr Joanne and Rodgers, Dr Jean
Authors: Jennings, F. W., Gichuki, C. W., Kennedy, P. G. E., Rodgers, J., Hunter, C. A., Murray, M., and Burke, J. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Neuropathology and Applied Neurobiology
Publisher:Wiley
ISSN:0305-1846
ISSN (Online):1365-2990

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