<i>In vitro</i> screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays

<p>Nanoparticles (NPs) may translocate to the brain following inhalation or oral exposures, yet higher throughput methods to screen NPs for potential neurotoxicity are lacking. The present study examined effects of 5 CeO<sub>2</sub> (5– 1288 nm), and 4 TiO<sub>2</sub> (6–142 nm) NPs and microparticles (MP) on network function in primary cultures of rat cortex on 12 well microelectrode array (MEA) plates. Particles were without cytotoxicity at concentrations ≤50 µg/ml. After recording 1 h of baseline activity prior to particle (3–50 µg/ml) exposure, changes in the total number of spikes (TS) and # of active electrodes (#AEs) were assessed 1, 24, and 48 h later. Following the 48 h recording, the response to a challenge with the GABA<sub>A</sub> antagonist bicuculline (BIC; 25 µM) was assessed. In all, particles effects were subtle, but 69 nm CeO<sub>2</sub> and 25 nm TiO<sub>2</sub> NPs caused concentration-related decreases in TS following 1 h exposure. At 48 h, 5 and 69 nm CeO<sub>2</sub> and 25 and 31 nm TiO<sub>2</sub> decreased #AE, while the two MPs increased #AEs. Following BIC, only 31 nm TiO<sub>2</sub> produced concentration-related decreases in #AEs, while 1288 nm CeO<sub>2</sub> caused concentration-related increases in both TS and #AE. The results indicate that some metal oxide particles cause subtle concentration-related changes in spontaneous and/or GABA<sub>A</sub> receptor-mediated neuronal activity <i>in vitro</i> at times when cytotoxicity is absent, and that MEAs can be used to screen and prioritize nanoparticles for neurotoxicity hazard.</p>