Repeated Pro-inflammatory stimuli: How does it affect demyelination and remyelination.

MURTA, VERONICA; PITOSSI, FERNANDO; FERRARI, CARINA

Huerta Grande, Córdoba, Argentina.

Taller; 1ra Reunión Conjunta de Neurociencias; 2009

Sociedad Argentina de Neurociencias

MS is a neurodegenerative disease characterized by demyelination, inflammation and axonal loss. Remyelination occurs in the early stages of the disease, but as the disease progresses remyelination fails. The most predominant type of MS exhibits relapsing-remitting episodes,  and remyelination is less efficient after every relapse. Patients in  relapsing phase show high levels of IL-1b in the CSF, and blocking it reduces the severity of the disease. We have observed that chronic expression of IL-1b in the striatum produces reversible demyelination, BBB breakdown and axonal damage. Our hypothesis is that repeated pro-inflammatory stimulus in the brain could exacerbate demyelination and/or impair remyelination in animals which have received a previous demyelinating stimulus. To contrast this hypothesis, we administered either adenoviral vectors expressing IL-1b (AdIL-1b), or other inflammatory stimulus (LPS). At different time points, we re-administered the AdIL-1b. Animals receiving pro-inflammatory stimuli twice had less inflammation and demyelination if the second stimulus was administrated during the resolution phase. However, when the second pro-inflammatory stimulus was given after the lesion´s resolution, inflammation and demyelination levels were similar to  control group. We observed that the glial activation followed the pattern of inflammation in all cases. We also found  up-regulation of oligodendrocyte lineage marker Olig2 21 days after the AdIL-1b injection, that decreased at day 30, and even more at 51. In conclusion,  a previous pro-inflammatory stimulus may reduce the inflammatory and demyelinating effect of a second pro-inflammatory stimulus, when administered in a specific point of the injury’s resolution.