High frequency stimulation of the subthalamic nucleus impacts adult neurogenesis in a rat model of Parkinson's disease

Khaindrava, V. G.; Salin, Pascal; Melon, Christophe; Ugrumov, M. V.; Goff, Lydia Kerkerian‐Le; Daszuta, Annie

doi:10.1016/j.nbd.2011.01.018

Cited by 34 publications

(33 citation statements)

References 59 publications

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“…59 In a 6-OHDA rat model of PD, STN-HFS was shown to induce changes on adult brain neurogenesis, increasing cell survival of newly formed cells in the olfactory bulb, in the dentate gyrus of the hippocampus, and rescue of dopamine in the striatum of lesioned rats. 60 Our results showing that STN-HFS significantly increased cell proliferation index within the striatal graft and also in regions of constitutive neurogenesis, such as the RMS, are consistent with those reports. Taken together, there is robust evidence in the literature supporting a key role for electrical activity in the maturation of neuronal progenitors in vitro, but also in physiological neurogenesis.…”

Section: Electric-neurogenic Coupling and Future Perspectivessupporting

confidence: 92%

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Furlanetti

Cordeiro

et al. 2015

Neurorehabil Neural Repair

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Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft-host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.

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Section: Electric-neurogenic Coupling and Future Perspectivessupporting

confidence: 92%

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Furlanetti

Cordeiro

et al. 2015

Neurorehabil Neural Repair

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“…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 .…”

Section: Glial-activation Challenges and Design Considerationsmentioning

confidence: 99%

Glial responses to implanted electrodes in the brain

et al. 2017

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The use of implants that can electrically stimulate or record electrophysiological or neurochemical activity in nervous tissue is rapidly expanding. Despite remarkable results in clinical studies and increasing market approvals, the mechanisms underlying the therapeutic effects of neuroprosthetic and neuromodulation devices, as well as their side effects and reasons for their failure, remain poorly understood. A major assumption has been that the signal-generating neurons are the only important target cells of neural-interface technologies. However, recent evidence indicates that the supporting glial cells remodel the structure and function of neuronal networks and are an effector of stimulation-based therapy. Here, we reframe the traditional view of glia as a passive barrier, and discuss their role as an active determinant of the outcomes of device implantation. We also discuss the implications that this has on the development of bioelectronic medical devices.

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“…In terms of supporting evidence from animal studies of neuroplasticity following DBS, one recent animal study showed increased new cell survival in the rostral migratory stream, including the hippocampus, and the olfactory bulb [12]. These finding are of great importance for a number of factors including the preclinical manifestation of olfactory dysfunction as well as its high prevalence rate.…”

Section: Discussionmentioning

confidence: 90%

“…Some insight has come from a rat study using the 6-OHDA model of Parkinson’s disease showing that prolonged high frequency stimulation of the STN has a neurorestorative action [12]. This finding suggests that DBS can change brain connectivity, corroborating previous findings from a human case study which, using diffusion tensor imaging (DTI) in PD, has demonstrated that DBS in the pedunculopontine nucleus (PPN) has a restorative action and increases connectivity of the PPN with the cerebellum [13].…”

Section: Introductionmentioning

confidence: 99%

Neural Plasticity in Human Brain Connectivity: The Effects of Long Term Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease

et al. 2014

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BackgroundPositive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson’s Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity.ResultsWe found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson’s Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson’s Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms.ConclusionsThe findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.

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High frequency stimulation of the subthalamic nucleus impacts adult neurogenesis in a rat model of Parkinson's disease

Cited by 34 publications

References 59 publications

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Glial responses to implanted electrodes in the brain

Neural Plasticity in Human Brain Connectivity: The Effects of Long Term Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease

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