Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 100, Issue 3, pages 747–757, February 2007
How to Cite
Hakkoum, D., Stoppini, L. and Muller, D. (2007), Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures. Journal of Neurochemistry, 100: 747–757. doi: 10.1111/j.1471-4159.2006.04257.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received June 15, 2006; revised manuscript received September 18, 2006; accepted September 26, 2006.
- organotypic hippocampal slice culture;
Interleukin (IL)-6 is a pro-inflammatory cytokine now widely recognized to contribute to the molecular events that follow CNS injury. Little is known, however, about its action on axonal sprouting and regeneration in the brain. We addressed this issue using the model of transection of Schaffer collaterals in mice organotypic hippocampal slice cultures. Transection of slice cultures was associated with a marked release of IL-6 that could be neutralized by an IL-6 blocking antibody. We monitored functional recovery across the lesion by recording synaptic responses using a multi-electrode array. We found that application of IL-6 antibodies to the cultures after lesioning significantly reduced functional recovery across the lesion. Furthermore, the level of expression of the 43-kDa growth-associated protein (GAP-43) was lower in slices treated with the IL-6 neutralizing antibody than in those treated with a control IgG. Conversely, addition of exogenous IL-6 to the culture medium resulted in a dose-dependent enhancement of functional recovery across the lesion and a higher level of expression of GAP-43. Co-culture of CA3 hemi-slices from thy1-YFP mice with CA1 hemi-slices from wild-type animals confirmed that IL-6-treated co-cultures exhibited an increased number of growing fluorescent fibres across the lesion site. Taken together these data indicate that IL-6 plays an important role in CNS repair mechanisms by promoting regrowth and axon regeneration.