Chronic sodium salicylate treatment exacerbates brain neurodegeneration in rats infected with Trypanosoma brucei.
We have reported previously that axonal degeneration in specific brain regions occurs in rats infected with the parasite Trypanosoma brucei. These degenerative changes occur in spatiotemporal association with over-expression of pro-inflammatory cytokine messenger RNAs in the brain. To test how aspirin-like anti-inflammatory drugs might alter the disease process, we fed trypanosome-infected rats with 200mg/kg of sodium salicylate (the first metabolite of aspirin) daily in their drinking water. Sodium salicylate treatment in uninfected rats did not cause any neural damage. However, sodium salicylate treatment greatly exacerbated neurodegeneration in trypanosome-infected rats, resulting in extensive terminal and neuronal cell body degeneration in the cortex, hippocampus, striatum, thalamus, and anterior olfactory nucleus. The exaggerated neurodegeneration, which occurred in late stages of infection, was temporally and somewhat spatially associated with a late-appearing enhancement of messenger RNA expression of interleukin-1beta, interleukin-1beta converting enzyme, tumor necrosis factor-alpha, and inhibitory factor kappaBalpha in the brain parenchyma. Restricted areas showed elevations in messenger RNA expression of interleukin-1 receptor antagonist, interleukin-6, inducible nitric oxide synthase, interferon-gamma, and inducible cyclooxygenase. The association suggests that increased production of pro-inflammatory cytokines in the brain may be an underlying mechanism for neural damage induced by the chronic sodium salicylate treatment. Furthermore, the results reveal a serious complication in using aspirin-like drugs for the treatment of trypanosome infection.
Quan
N
N
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Mhlanga
J D
JD
Whiteside
M B
MB
Kristensson
K
K
Herkenham
M
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012980:Sodium Salicylate / Q000494:pharmacology*; D013997:Time Factors; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D012333:RNA, Messenger; D012980:Sodium Salicylate