Development of a stretch-induced neurotrauma model for medium-throughput screening in vitro: identification of rifampicin as a neuroprotectant

We hypothesized that an in vitro, stretch-based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma. Experimental approach: We screened three neural cell lines (B35, RN33B and SH-SY5Y) subjected to two differentiation

We hypothesized that an in vitro, stretch-based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma. Experimental approach: We screened three neural cell lines (B35, RN33B and SH-SY5Y) subjected to two differentiation

From screening of a composite library of 3500 drugs, five drugs (when applied in a post-treatment regimen relative to stretch injury) improved both LDH and MTT responses. The effects of rifampicin were investigated in further detail. Rifampicin reduced cell necrosis and apoptosis and improved cellular bioenergetics. In a second model (stretch injury in human stem cell-derived neurons), rifampicin pretreatment attenuated LDH release, protected against the loss of neurite length and maintained neuron-specific class III β-tubulin immunoreactivity. Conclusions and implications: We conclude that the current model is suitable for medium-throughput screening to identify compounds with neuroprotective potential. Rifampicin, when applied either in pre- or post-treatment, improves the viability of neurons subjected to stretch injury and protects against neurite loss. Rifampicin may be a candidate for repurposing for the therapy of traumatic brain injury. Linked articles: This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.