Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats
2023
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Authors:
Lazarević, MilicaStegnjaić, Goran
Jevtić, Bojan
Stanisavljević, Suzana
Nikolovski, Neda
Momčilović, Miljana
Dimitrijević, Mirjana
Miljković, Đorđe
Contributors
Kanazir, SelmaSavić, Danijela
Document Type:
Conference object (Published version)
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© 2023 by Serbian Neuroscience Society and associates.
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Show full item recordAbstract:
Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Kanazir S, Savić D, editors. Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2023. p. 42.