Chronic sodium salicylate treatment exacerbates brain neurodegeneration inrats infected with Trypanosoma brucei

Citation
N. Quan et al., Chronic sodium salicylate treatment exacerbates brain neurodegeneration inrats infected with Trypanosoma brucei, NEUROSCIENC, 96(1), 2000, pp. 181-194
Citations number
54
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROSCIENCE
ISSN journal
03064522 → ACNP
Volume
96
Issue
1
Year of publication
2000
Pages
181 - 194
Database
ISI
SICI code
0306-4522(2000)96:1<181:CSSTEB>2.0.ZU;2-Q
Abstract
We have reported previously that axonal degeneration in specific brain regi ons occurs in rats infected with the parasite Trypanosoma brucei. These deg enerative changes occur in spatiotemporal association with over-expression of pro-inflammatory cytokine messenger RNAs in the brain. To test how aspir in-like anti-inflammatory drugs might alter the disease process, we fed try panosome-infected rats with 200 mg/kg of sodium salicylate (the first metab olite of aspirin) daily in their drinking water. Sodium salicylate treatmen t in uninfected rats did not cause any neural damage. However, sodium salic ylate treatment greatly exacerbated neurodegeneration in trypanosome-infect ed rats, resulting in extensive terminal and neuronal cell body degeneratio n in the cortex, hippocampus, striatum, thalamus, and anterior olfactory nu cleus. The exaggerated neurodegeneration, which occurred in late stages of infection, was temporally and somewhat spatially associated with a late-app earing enhancement of messenger RNA expression of interleukin-1 beta, inter leukin-1 beta converting enzyme, tumor necrosis factor-alpha, and inhibitor y factor kappa B alpha in the brain parenchyma. Restricted areas showed ele vations in messenger RNA expression of interleukin-1 receptor antagonist, i nterleukin-6, inducible nitric oxide synthase, interferon-gamma, and induci ble cyclooxygenase. The association suggests that increased production of pro-inflammatory cyto kines in the brain may be an underlying mechanism for neural damage induced by the chronic sodium salicylate treatment. Furthermore, the results revea l a serious complication in using aspirin-like drugs for the treatment of t rypanosome infection. Published by Elsevier Science Ltd.