Increased Precursor Cell Proliferation after Deep Brain Stimulation for Parkinson's Disease: A Human Study

Abstract

ObjectiveDeep brain stimulation (DBS) has been used for more than a decade to treat Parkinson's disease (PD); however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the “germinal niches,” we sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly.MethodsWe studied the brains of a total of 12 idiopathic Parkinson's disease patients that were treated with DBS (the electrode placement occurred 0.5–6 years before death), and who subsequently died of unrelated illnesses. These were compared to the brains of 10 control individuals without CNS disease, and those of 5 PD patients with no DBS.ResultsImmunohistochemical analyses of the subventricular zone (SVZ) of the lateral ventricles, the third ventricle lining, and the tissue surrounding the DBS lead revealed significantly greater numbers of proliferating cells expressing markers of the cell cycle, plasticity, and neural precursor cells in PD-DBS tissue compared with both normal brain tissue and tissue from PD patients not treated with DBS. The level of cell proliferation in the SVZ in PD-DBS brains was 2–6 fold greater than that in normal and untreated PD brains.ConclusionsOur data suggest that DBS is capable of increasing cellular plasticity in the brain, and we hypothesize that it may have more widespread effects beyond the electrode location. It is unclear whether these effects of DBS have any symptomatic or other beneficial influences on PD.

Glial responses to implanted electrodes in the brain

“…In the context of neurogenesis, neuromodulation is gaining traction as a reparative tool for brain injury and disease 118,134 . Neurostimulation stimulates neural progenitor proliferation 135–137 , directs the migration (galvanotaxis) of neuronal and glial precursors 134,138–140 and promotes their differentiation 136,137,140,141 . Interestingly, tDCS-polarized proinflammatory microglia accompany NG2-precursor migration to promote functional recovery after stroke 130 .…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…At the present time there is no strong evidence from the human literature for a disease-modifying effect of DBS, although a recent study suggests that such effects may occur [317].…”

Mechanisms of action underlying the efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson's disease: central role of disease severity

“… Both cholinergic and glutamatergic pathways provide an extensive contribution to the effectiveness of movement and associative learning, as seminally clarified by studies on PPN‐fugal axons and on thalamostriatal impingement (Wall et al ., ; Huerta‐Ocampo et al ., ). STN‐DBS indeed promotes immediate effects not interpretable in light of standard mechanisms of synaptic release and circuitry, but possibly attributable to three orders of sudden mechanisms: (i) brutal reorganization of band frequencies (Fig. ); (ii) fast change of cellular products as nucleotides (cGMP/cAMP, Stefani et al ., , ,); (iii) possible alterations of microglial states of activation (Vedam‐Mai et al ., ).

Hypothetical concurrent mechanisms playing a role in the interaction between DBS and disease progression.

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