Peripheral inflammation and neuroprotection: systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease.
Complete Freund's adjuvant (CFA), a pro-inflammatory agent, was inoculated, subcutaneously, to Sprague-Dawley rats prior to the intrastriatal injection of 6-hydroxydopamine (6-OHDA). Animals were sacrificed 7 and 28 days following 6-OHDA injection; neuronal damage, glial activation and cytokine levels, within the nigrostriatal system, were then investigated. Nigrostriatal degeneration induced by 6-OHDA was accompanied by early microglial and astroglial activation, which preceded the onset of dopaminergic cell loss, in the SNc, without significant changes in cytokine levels. CFA pretreatment markedly reduced the SNc neuronal loss and associated microglial activation, as well as the rotational response to apomorphine. These changes were associated with moderate, transient increases in the nigrostriatal levels of glial-cell-derived neurotrophic factor (GDNF) and pro-inflammatory cytokines, including interleukin (IL)-1alpha, IL-1beta and IL-6. Our results show that prior delivery of a peripheral, pro-inflammatory stimulus induces neuroprotection, in a rodent model of Parkinson's disease, possibly through the modulation of cytokine production at the nigrostriatal level.
Armentero
Marie-Thérèse
MT
Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino, Via Mondino, 2 27100 Pavia, Italy.
Levandis
Giovanna
G
Nappi
Giuseppe
G
Bazzini
Eleonora
E
Blandini
Fabio
F
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology* / Q000473:pathology; D018696:Neuroprotective Agents / Q000276:immunology* / Q000627:therapeutic use; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D018696:Neuroprotective Agents; D016627:Oxidopamine; D005620:Freund's Adjuvant