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Title

Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures

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Published in Journal of Neurochemistry. 2007, vol. 100, no. 3, p. 747-757
Abstract 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.
Keywords AnimalsAntibodies/pharmacologyAxotomyBrain Damage, Chronic/drug therapy/immunology/physiopathologyCoculture TechniquesDose-Response Relationship, DrugGAP-43 Protein/metabolismGrowth Cones/drug effects/ metabolismHippocampus/cytology/drug effects/immunologyInterleukin-6/antagonists & inhibitors/immunology/ pharmacologyMiceMice, Inbred C57BLMice, TransgenicNerve Growth Factors/immunology/pharmacology/therapeutic useNerve Regeneration/drug effects/ immunologyNeuronal Plasticity/drug effects/ immunologyOrgan Culture TechniquesRecovery of Function/drug effects/ immunologySynaptic Transmission/drug effects/immunology
Stable URL http://archive-ouverte.unige.ch/unige:10294
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PMID: 17144903
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