The impact of subthalamic deep brain stimulation on nigral neuroprotection-myth or reality?

OBJECTIVE

In the present review article we summarize available clinical and preclinical evidence, if modulation of the subthalamic nucleus (STN) could be a target for neuroprotection in Parkinson's disease (PD).

BACKGROUND

Chronic deep brain stimulation (DBS) of the STN has emerged as a powerful therapeutic alternative for the treatment of PD, ensuring stable symptom control for up to five years despite the progressive nature PD.

MATERIALS AND METHODS

Comparative review of literature in PuBMed available up to December 2008.

RESULTS

The assessment of neuroprotection has been proven difficult in the clinical situation, as medical or surgical therapeutic options that improve PD symptoms could be erroneously considered to be neuroprotective because of the difficulty of differentiating between symptomatic effects and potential neuromodulative disease-related effects of various treatment options applied in PD. The methodological limitations of clinical trials underline the importance of putative neuroprotective compounds to be tested in clinically driven preclinical studies. Thus, animal models, mimicking progressive nigrostriatal cell death, are indispensable to further advance the important issue of neuroprotection or neuromodulation following DBS.

CONCLUSION

Clear clinical evidence for STN-DBS-related neuroprotection in PD is missing. However, numerous preclinical studies show (and are discussed) that silencing of the STN via lesion or DBS may exert neuromodulative effects on nigral dopamine neurons.