Predictability of thermo-lesions using electrodes for deep brain stimulation - an in vitro study

AbstractDeep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

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Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach

10.1101/2021.11.27.470141 ◽

2021 ◽

Author(s):

Chih-Lun Su ◽

Ping-Hsiang Yen ◽

Chao-Chun Cheng ◽

Po-Han Chiang

Keyword(s):

Deep Brain Stimulation ◽

Magnetic Fields ◽

Brain Stimulation ◽

Transient Receptor Potential ◽

Genetic Manipulation ◽

Biological Tissues ◽

Physical Stimulation ◽

Deep Brain

Various physical stimulation methods are developed to minimize the invasiveness of deep brain stimulation (DBS). Among them, only magnetic field can penetrate into the biological tissues without scattering or absorption, which makes it ideal for untethered DBS. Recently developed magnetogenetics have shown the potential of developing treatments for neurological disorders. However, magnetogenetic approaches have potential side effects from overexpression of exogenous ion channels and gene delivery with viral vectors. Here, we demonstrated that the iron oxide magnetic nanodiscs (~270 nm) can be used as transducers to trigger calcium responses in the wild-type cultured neurons during the application of slow varying weak magnetic fields (50 mT at 10 Hz). Moreover, we identified that the intrinsic mechanosensitive ion channel transient receptor potential canonical (TRPC), which were widely expressed in the brain, plays the main roles in this magnetomechanical stimulation. Finally, when we applied magnetic fields to the awake mice with magnetic nanodiscs injecting into subthalamic nucleus, the magnetomechanical stimulation triggered neuronal activities in the targeted region and the downstream region. Overall, this research demonstrated a magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in awake mice in vivo without implants or genetic manipulation.

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Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro

NeuroMolecular Medicine ◽

10.1007/s12017-021-08674-y ◽

2021 ◽

Author(s):

Carolin Kubelt ◽

Henri Molkewehrum ◽

Ralph Lucius ◽

Michael Synowitz ◽

Janka Held-Feindt ◽

...

Keyword(s):

Electrical Stimulation ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Inflammatory Mediators ◽

Messenger Rna ◽

Quantitative Polymerase Chain Reaction ◽

Protein Levels ◽

Vitro Model ◽

Deep Brain

AbstractDeep brain stimulation (DBS) seems to modulate inflammatory processes. Whether this modulation leads to an induction or suppression of inflammatory mediators is still controversially discussed. Most studies of the influence of electrical stimulation on inflammation were conducted in rodent models with direct current stimulation and/or long impulses, both of which differ from the pattern in DBS. This makes comparisons with the clinical condition difficult. We established an in-vitro model that simulated clinical stimulation patterns to investigate the influence of electrical stimulation on proliferation and survival of human astroglial cells, microglia, and differentiated neurons. We also examined its influence on the expression of the inflammatory mediators C-X-C motif chemokine (CXCL)12, CXCL16, CC-chemokin-ligand-2 (CCL)2, CCL20, and interleukin (IL)-1β and IL-6 by these cells using quantitative polymerase chain reaction. In addition, protein expression was assessed by immunofluorescence double staining. In our model, electrical stimulation did not affect proliferation or survival of the examined cell lines. There was a significant upregulation of CXCL12 in the astrocyte cell line SVGA, and of IL-1β in differentiated SH-SY5Y neuronal cells at both messenger RNA and protein levels. Our model allowed a valid examination of chemokines and cytokines associated with inflammation in human brain cells. With it, we detected the induction of inflammatory mediators by electrical stimulation in astrocytes and neurons.

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Reduction of Magnetic Resonance Imaging-related Heating in Deep Brain Stimulation Leads Using a Lead Management Device

Operative Neurosurgery ◽

10.1227/01.neu.0000176877.26994.0c ◽

2005 ◽

Vol 57 (suppl_4) ◽

pp. ONS-392-ONS-397 ◽

Cited By ~ 22

Author(s):

Kenneth B. Baker ◽

Jean Tkach ◽

John D. Hall ◽

John A. Nyenhuis ◽

Frank G. Shellock ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Deep Brain Stimulation ◽

Magnetic Resonance ◽

Brain Stimulation ◽

Small Diameter ◽

Burr Hole ◽

Resonance Imaging ◽

Lead Management ◽

Deep Brain

Abstract OBJECTIVE: To evaluate the ability of a lead management device to reduce magnetic resonance imaging (MRI)-related heating of deep brain stimulation (DBS) leads and thereby to decrease the risks of exposing patients with these implants to MRI procedures. METHODS: Experiments were performed using the Activa series (Medtronic, Inc., Minneapolis, MN) DBS systems in an in vitro, gelled-saline head and torso phantom. Temperature change was recorded using fluoroptic thermometry during MRI performed using a transmit-and-receive radiofrequency body coil at 1.5 T and a transmit-and-receive radiofrequency head coil at 3 T. A cranial model placed in the phantom was used to test a custom-designed burr hole device that permitted the placement of small-diameter, concentric loops around the burr hole at the DBS lead as it exited the cranium. RESULTS: A total of 41 scans were performed, with absolute temperature changes ranging from 0.8 to 10.3°C. Depending on the MRI system tested and the side of the phantom on which the hardware was placed, loop placement resulted in reductions in temperature rise of 41 to 74%. The effect was linearly related to the number of loops formed (P < 0.01) over the range tested (0–2.75 loops). CONCLUSION: Small, concentric loops placed around the burr hole seem to reduce MRI-related heating for these implants. Although the mechanism is still not fully understood, a device such as that used in the present study could permit a wider range of clinical scanning sequences to be used at 1.5 and 3 T in patients with DBS implants, in addition to increasing the margin of safety for the patient.

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