Identifying the Therapeutic Effects and Mechanisms of Innovative Transcranial Burst Electrostimulation in a Rat Model of Parkinson'S Disease: a Feasibility Study

Parkinson's disease (PD) is recognized as the progressive age-related neurodegenerative disorder which affects an estimated 6 million people worldwide and will affect double to over 12 million by 2040. The common characteristic underlying pathology of PD is a nigrostriatal dopaminergic neuron loss, leading to motor and non-motor functional deficits. Currently, there is no cure for PD, but the medications (e.g. Levodopa) or surgical approaches (e.g. deep brain stimulation, DBS) can relieve the symptoms of PD. However, long‐term use of levodopa is often complicated by motor fluctuations or L-DOPA-induced dyskinesia (LID). DBS has few disadvantages with the high cost of surgical procedures, the risk of infection and lead displacement, which may decrease the efficacy over time. Thus, it is still a high unmet clinical need for developing the advanced, alternative and nonpharmacological therapeutic approach that can overcome the limitations of current therapies for PD. A number of alternative neuromodulation procedures such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) have been suggested as new therapeutic strategies for PD. To enhance the neuromodulation effects, we have developed a novel stimulation scheme, termed transcranial burst electrostimulation (tBES), which can provide the electrostimulation by combining a tDCS and theta burst stimulation (TBS) and has been initially identified having more efficiently to induce the neural plasticity. In this proposed study, we will further identify the therapeutic values of such a stimulation scheme for PD under preclinical animal research. It will be helpful for serving as a translational platform to further confirm the therapeutic mechanisms of tBES for PDTo achieve these goals, we will apply an acute neurotoxic PD rat model and evaluate the therapeutic potential of tBES. In the proposed study, we will (1) identify the neuromodulation effect of tBES in vivo rat model; (2) design the long-term implantable tBES module for stimulating the primary motor cortex in freely moving PD rats; (3) adapt tBES to evaluate the responses of tBES-elicited plasticity and extracellular dopamine concentration after NIDBS in PD animals; (4) validate and optimize the beneficial effects of tBES protocol in motor (e.g., locomotor function, rigidity, tremor, akinesia and gait pattern) and non-motor (depression, anxiety, recognition memory loss) deficits following long-term treatment of tBES in PD rats; (5) perform the biochemistry analysis (e.g. IHC and Western blot) to verify the anti-inflammation, antiapoptosis and neuroprotection effects after tBES treatment in PD rats.This integrated neurorehabilitation and neuroengineering approaches will provide a unique opportunity to identify the effects of neuroplasticity, neuromodulation as well as the motor and non-motor symptoms following tBES treatment in the basic research of PD, which may enhance for the promising possibility of the potential use of tBES for PD or other neurological disorders.

Project ID:PC10907-1555
External Project ID:MOST109-2314-B182-029-MY3