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Facilitating Drug Discovery: An Automated High-content Inflammation Assay in Zebrafish
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Therapeutic potential of new antiinflammatory drugs

Annamaria Vezzani1, Tamas Bartfai, Marco Bianchi

  • 1Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, Milan, Italy. vezzani@marionegri.it

Epilepsia
|October 5, 2011
PubMed

Experimental and clinical findings have shown in the past decade that specific proinflammatory mediators and their cognate receptors are upregulated in epileptic brain tissue. In particular, the IL-1 receptor (R)/Toll-like receptor (TLR) signaling pathways are activated in experimental models of seizures and in human epileptic tissue from drug-resistant patients. Pharmacological targeting of these proinflammatory pathways using selective receptor antagonists, or the use of transgenic mice with perturbed cell signaling, demostrated that the activation of IL-1R type 1 and TLR4 by their respective endogenous ligands, i.e., interleukin (IL)-1b and High Mobility Group Box 1, is implicated in the precipitation and recurrence of experimentally induced seizures in rodents. This evidence highlights a new target system for pharmacological intervention to inhibit seizures by interfering with mechanisms involved in their genesis and recurrence.

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