Electrical stimulation of the subthalamic nucleus (STN) is clinically employed to ameliorate several symptoms of manifest Parkinson’s Disease (PD). Stimulation parameters utilized by chronically implanted pulse generators comprise biphasic rectangular short (60–100 μs) pulses with a repetition frequency between 130 and 180 Hz. A better insight into the effect of electrical stimulation parameters could potentially reveal new possibilities for the improvement of deep brain stimulation (DBS) as a treatment. To this end, we employed single-sided 6-hydroxidopamine (6-OHDA) lesioning of the medial forebrain bundle (MFB) in rats to systematically investigate alternative stimulation parameters. These hemi-parkinsonian (hemi-PD) rats underwent individualized, ipsilateral electrical stimulation to the STN of the lesioned hemisphere, while the transiently induced contralateral rotational behavior was quantified to assess the effect of DBS parameter variations. The number of induced rotations during 30 s of stimulation was strongly correlated with the amplitude of the stimulation pulses. Despite a general linear relation between DBS frequency and rotational characteristics, a plateau effect was observed in the rotation count throughout the clinically used frequency range. Alternative waveforms to the conventional biphasic rectangular ( Rect ) pulse shapes [Triangular ( Tri ), Sinusoidal ( Sine ), and Sawtooth ( Lin.Dec. )] required higher charges per phase to display similar behavior in rats as compared to the conventional pulse shape. The Euclidean Distance (ED) was used to quantify similarities between different angular trajectories. Overall, our study confirmed that the effect of different amplitude and frequency parameters of STN-DBS in the hemi-PD rat model was similar to those in human PD patients. This shows that induced contralateral rotation is a valuable readout in testing stimulation parameters. Our study supports the call for more pre-clinical studies using this measurement to assess the effect of other DBS parameters such as pulse-width and interphase intervals.

A wise selection of tracers is critical for magnetic particle imaging (MPI). Most of the current tracers are based on superparamagnetic iron oxide nanoparticles (SPIONs) with a suitable coating. We prepared maghemite cores (γ-Fe2O3) by coprecipitation of Fe(II) and Fe(III) salts with ammonium hydroxide followed by oxidation with hydrogen peroxide and stabilization as an anionic (γ-Fe2O3⊖) or cationic colloid (γ-Fe2O3⨁). The cores were coated by poly(N-(2-hydroxypropyl)methacrylamide)-co-N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide. The particles were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, Mössbauer spectroscopy, tested in vitro in a field-free point MPI scanner, and compared to nanoparticles prepared by oxidation with sodium hypochlorite and to the commercially available Resovist®. The cores had an average diameter of 8.0 nm (γ-Fe2O3⨁) and 8.7 nm (γ-Fe2O3⊖); the hydrodynamic diameter was 88 nm. Zeta potential values for both positively charged (+52 mV) and negatively charged particles (–60 mV) provided for good colloidal stabilization. Spinel structure of maghemite was confirmed by Mössbauer spectroscopy. The uncoated γ-Fe2O3⨁ particles yielded an MPI signal lower (by 16 %) than Resovist; the coated ones reached 88 % of the Resovist signal. Anionic γ-Fe2O3⊖ particles reached a higher (uncoated particles, by 15 %) or comparable (coated ones) signal relative to Resovist with a substantially lower signal dispersion. Control particles prepared by oxidation with sodium hypochlorite scored the weakest results. To conclude, a suitable size, narrow size distribution, and colloidal stability predispose the synthetized particles for use as a tracer for MPI. The anionic particles provided a higher signal with a lower dispersion than commercial tracers.

Cortico-basal ganglia beta oscillations (13–30 Hz) are assumed to be involved in motor impairments in Parkinson’s Disease (PD), especially in bradykinesia and rigidity. Various studies have utilized the unilateral 6-hydroxydopamine (6-OHDA) rat PD model to further investigate PD and test novel treatments. However, a detailed behavioral and electrophysiological characterization of the model, including analyses of popular PD treatments such as DBS, has not been documented in the literature. We hence challenged the 6-OHDA rat hemi-PD model with a series of experiments (i.e., cylinder test, open field test, and rotarod test) aimed at assessing the motor impairments, analyzing the effects of Deep Brain Stimulation (DBS), and identifying under which conditions excessive beta oscillations occur. We found that 6-OHDA hemi-PD rats presented an impaired performance in all experiments compared to the sham group, and DBS could improve their overall performance. Across all the experiments and behaviors, the power in the high beta band was observed to be an important biomarker for PD as it showed differences between healthy and lesioned hemispheres and between 6-OHDA-lesioned and sham rats. This all shows that the 6-OHDA hemi-PD model accurately represents many of the motor and electrophysiological symptoms of PD and makes it a useful tool for the pre-clinical testing of new treatments when low β (13–21 Hz) and high β (21–30 Hz) frequency bands are considered separately.

Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.

Electric stimulators with precise and reliable outputs are an indispensable part of electrophysiological research. From single cells to deep brain or neuromuscular tissue, there are diverse targets for electrical stimulation. Even though commercial systems are available, we state the need for a low-cost, high precision, functional, and modular (hardware, firmware, and software) current stimulation system with the capacity to generate stable and complex waveforms for pre-clinical research. The system presented in this study is a USB controlled 4-channel modular current stimulator that can be expanded and generate biphasic arbitrary waveforms with 16-bit resolution, high temporal precision (µs), and passive charge balancing: the NES STiM (Neuro Electronic Systems Stimulator). We present a detailed description of the system's structural design, the controlling software, reliability test, and the pre-clinical studies [deep brain stimulation (DBS) in hemi-PD rat model] in which it was utilized. The NES STiM has been tested with MacOS and Windows operating systems. Interfaces to MATLAB source codes are provided. The system is inexpensive, relatively easy to build and can be assembled quickly. We hope that the NES STiM will be used in a wide variety of neurological applications such as Functional Electrical Stimulation (FES), DBS and closed loop neurophysiological research.