gms | German Medical Science

Objective: Parkinson's disease (PD) is a neurodegenerative disease leading to progressive and disabling deterioration of motor and cognitive skills. Current surgical treatment by deep brain stimulation (DBS) of the subthalamic nucleus (STN) can temporarily improve motor symptoms. Alternative regenerative approaches are under research to restitute dopaminergic neurotransmission and offer a more extensive and long lasting repair. However, sparse data are available concerning the combination of cell therapy and neuromodulation. The aim of our project was to test whether the high frequency stimulation within the STN can act synergistically with dopaminergic grafts in reversing functional deficits.

Method: Twenty adult rats were rendered parkinsonian by unilateral injection of 6-OHDA into the right medial forebrain bundle (MFB). The MFB lesioned animals were assigned into two groups. The “STN-DBS group” received additional ipsilateral STN long-term continuous high frequency stimulation. All animals were given primary striatal grafts of rat E14 ventral mesencephalic (VM) tissue into the right striatum. Drug-induced rotation, Cylinder and Stepping tests were performed to evaluate the effect of each intervention. Post-mortem immunohistochemistry was carried out to assess the lesions and the dopaminergic grafts.

Results: Functional recovery was observed in the behavioural tests in both groups after transplantation. Nevertheless, the “STN Group” showed better outcome than the “only-transplanted” group in all the behavioral tests (Drug-induced rotation test, p=0.047; Cylinder-test, p=0.009; Stepping-test, p=0.01). Survival of transplanted VM cells was observed in the striatum of both groups, however the histological evaluation (cell count and optical density) clearly revealed a positive effect of the STN modulation on the graft cell survival (p=0.017) and integration (p=0.002) within the host striatum.

Conclusions: Functional recovery and graft survival were observed after striatal transplantation, and improved by means of STN stimulation. The read-outs as graft survival and host re-innervation, and behavioural recovery (in freely moving animals during stimulation) presented so far showed that dopaminergic grafts and DBS can act synergistically in the experimental model of PD. These findings suggest that cell therapy could be combined with other techniques of STN modulation such as DBS. Further studies should be performed to confirm and extend these findings.