Microelectrode Arrays Modified with Nanocomposites for Monitoring Dopamine and Spike Firings under Deep Brain Stimulation in Rat Models of Parkinson's Disease.

Abstract

Little is known about the efficacy of deep brain stimulation (DBS) as an effective treatment for Parkinson's Disease (PD) because of the lack of multichannel neural electrical and chemical detection techniques at the cellular level. In this study, a 7-mm-long and 250-μm-wide microelectrode array (MEA) was fabricated to provide real-time monitoring of dopamine (DA) concentration and neural spike firings in the caudate putamen (CPU) of rats with PD. Platinumn nanoparticles and reduced graphene oxide nanocomposites (Pt/rGO) were modified onto the sensitive microelectrode sites. The detection limit (50 nM) and sensitivity (8.251 pA/μM) met the specific requirements for DA detection in vivo. A single neural spike was isolated due to the high signal-to-noise ratio of the MEA. DBS was applied in the affected side of the globus pallidus internal (GPi) in PD rats. After DBS, the concentration of DA in the bilateral CPU increased markedly. The mean increment of the ipsilateral DA was 7.33 μM (increasing from 0.54 μM to 7.87 μM), which was 2.2-fold higher than the increment in the contralateral side. The mean amplitude of neural spikes in the bilateral CPU decreased more than 10%, and was more obvious in the ipsilateral side where the spike amplitude changed from 169 μV to 134 μV. Spike firing rate decreased by 65% (ipsilateral side) and 51% (contralateral side). The power of the local field potential decreased to 940 μW (ipsilateral side) and 530 μW (contralateral side) in 0-30 Hz. Collectively, our data show that the GPi-DBS plays a significant regulatory role in the bilateral CPU in terms of DA concentration, spike firing, and power; furthermore, the ipsilateral variations of the dual mode signals were more significant than those in the contralateral side. These results provide new detection and stimulation technology for understanding the mechanisms underlying Parkinson's disease and should, therefore, represent a useful resource for the design of future treatments.