Excitotoxicity In Vitro Assay Services for Stroke Drug Discovery & Development

Introduction to the Excitotoxicity and Stroke

Excitotoxicity is a specific type of neurotoxicity mediated by glutamate that may be the missing link between ischemia and neuronal death. Excitotoxicity has now been identified as a key mechanism in ischemic stroke, and intervening in the mechanistic steps leading to excitotoxicity can prevent stroke damage. Understanding how glutamate excitotoxicity works has far-reaching applications in the field of stroke and could help in the development of a new generation of excitotoxicity inhibitors.

Fig. 1. Excitotoxic seizures and transient MCAO cause similar differential gene regulation in tau−/− mice. (Bi et al., 2017)

Custom Excitotoxicity In Vitro Assay Services

Ace Therapeutics provides reliable excitotoxicity in vitro assay services to rapidly analyze the neuroprotective potential of stroke drug candidates. Our team of experts has characterized a range of cells associated with N-Methyl-D-aspartate (NMDA) or glutamate-induced cell death. By using these models, we can simulate the excitotoxic conditions observed in stroke and assess the effects of test compounds on neuronal viability and cytotoxicity.

Experimental Design

• Cell culture. A range of different neuronal cell models including immortalized neuroblastoma cells, primary mouse cortical neurons, and iPSC-derived excitatory neurons. Specific cell lines can be customized to meet customer needs.
• Pretreatment. Incubate rat primary neurons with test compounds 24 hours prior to L-glutamate injury.
• Glutamate induction. Cells are treated with L-glutamate for 24 hours. The concentration and time point of glutamate addition depends on cell type.
• Endpoint parameter measurements. After 24 hours of exposure, we could analyze different parameters related to all stages of the cell death process. Some of the endpoints we analyze include neuronal viability, LDH release, cell death, neurite outgrowth, caspase activation.

Why Choose Us

• By using fully characterized cell models and precisely controlled experimental conditions, we can obtain reliable and reproducible results in a relatively short period of time.
• We comprehensively assess multiple parameters associated with excitotoxic cell death.
• The assay platform we developed is suitable for high-throughput screening and facilitates the screening of large compound libraries to efficiently identify potential stroke drugs.

Ace Therapeutics leverages our excitotoxicity in vitro assay platform to perform high-throughput phenotypic cell screening using neuronal cell models to identify novel compounds that prevent glutamate-induced excitotoxicity. We aim to accelerate stroke drug discovery and development. Please do not hesitate to contact us!

1. Bi, M., Gladbach, et al. (2017). Tau exacerbates excitotoxic brain damage in an animal model of stroke. Nature communications, 8(1), 473.