Dopamine and Striatal Neuron Firing Respond to Frequency-Dependent DBS Detected by Microelectrode Arrays in the Rat Model of Parkinson’s Disease

(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level.

Widespread Striatal Delivery of GDNF from Encapsulated Cells Prevents the Anatomical and Functional Consequences of Excitotoxicity

Methods. Human ARPE-19 cells engineered to secrete high levels of the glial cell line-derived neurotrophic factor (GDNF) were encapsulated into hollow fiber membranes. The devices were implanted into the rat striatum 1 week prior to striatal quinolinic acid injections. Animals were evaluated using a battery of validated motor tests, and histology was performed to determine the extent of GDNF diffusion and associated prevention of neuronal cell loss and behavioral deficits. Results. Encapsulated cell-based delivery of GDNF produced widespread distribution of GDNF throughout the entire implanted striatum. Stereological estimates of striatal neuron number and volume of lesion size revealed that GDNF delivery resulted in near complete neuroprotection. Conclusions. Delivery of neurotrophic molecules such as GDNF using encapsulated cells has reached a technological point where clinical evaluation is justified. Because GDNF has been effective in animal models of Parkinson’s disease, stroke, epilepsy, and Huntington’s disease, among other debilitating neurodegenerative diseases, encapsulated cell-based delivery of GDNF might represent one innovative means of slowing the neural degeneration seen in a myriad of currently untreatable neurological diseases.