Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery

IEEE Transactions on Bio-medical Engineering
Jing LiuYevgeny Berdichevsky

Abstract

Hippocampal slice cultures spontaneously develop chronic epilepsy several days after slicing and are used as an in vitro model of post-traumatic epilepsy. Here, we describe a hybrid microfluidic-microelectrode array (μflow-MEA) technology that incorporates a microfluidic perfusion network and electrodes into a miniaturized device for hippocampal slice culture based antiepileptic drug discovery. Field potential simulation was conducted to help optimize the electrode design to detect a seizure-like population activity. Epilepsy-on-a-chip model was validated by chronic electrical recording, neuronal survival quantification, and anticonvulsant test. To demonstrate the application of μflow-MEA in drug discovery, we utilized a two-stage screening platform to identify potential targets for antiepileptic drugs. In Stage I, lactate and lactate dehydrogenase biomarker assays were performed to identify potential drug candidates. In Stage II, candidate compounds were retested with μflow-MEA-based chronic electrical assay to provide electrophysiological confirmation of biomarker results. We screened 12 receptor tyrosine kinases inhibitors, and EGFR/ErbB-2 and cFMS inhibitors were identified as novel antiepileptic compounds. This epilepsy-on...Continue Reading

Citations

Mar 10, 2020·Lab on a Chip·Yanan ZhaoPu Chen
Oct 5, 2019·Materials·Natasha Antill-O'BrienCathal D O'Connell
May 24, 2019·International Journal of Molecular Sciences·Jing LiuYevgeny Berdichevsky

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.