N. Quan et al., Chronic sodium salicylate treatment exacerbates brain neurodegeneration inrats infected with Trypanosoma brucei, NEUROSCIENC, 96(1), 2000, pp. 181-194
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.