Treatment Of Neural Disorders Research Articles

Neural modulation with photothermally active nanomaterials

Modulating neural electrophysiology with high precision is essential for understanding neural communication and for the diagnosis and treatment of neural disorders. Photothermal modulation offers a remote and non-genetic method for neural modulation with high spatiotemporal resolution and specificity. This technique induces highly localized and transient temperature changes at the cell membrane interfaced with photothermally active nanomaterials. This rapid temperature change affects the electrical properties of the cell membrane or temperature-sensitive ion channels. In this Review, we discuss the fundamental material properties and illumination conditions that are necessary for nanomaterial-assisted photothermal neural excitation and inhibition. We examine how this versatile technique allows direct investigation of neural electrophysiology and signalling pathways in two-dimensional and three-dimensional cell cultures and tissues, and highlight the scientific and technological challenges in terms of cellular specificity, light delivery and biointerface stability on the road to clinical translation. Photothermal modulation is a non-genetic approach for remote neural modulation with high spatiotemporal resolution and specificity. This Review summarizes the fundamental material properties and experimental conditions necessary for efficient nanomaterial-assisted photothermal excitation, inhibition and regulation of cellular signalling pathways.

Non-Hermitian complementary acoustic metamaterials for lossy barriers

Complementary materials are designed for the suppression of strongly mismatched potential barriers to enhance wave transmission and reduce wavefront distortion through the barriers. In acoustics, complementary materials enable noninvasive brain imaging and the treatment of neural disorders by overcoming the high impedance mismatch layer that prevents ultrasound transmission. However, the porous skull layer possesses intrinsic loss that prohibits the effective use of complementary metamaterials alone. Here, we propose to apply a non-Hermitian complementary metamaterial (NHCMM) to counteract the impedance mismatch and energy attenuation effect of the skull to achieve high acoustic transmission at high frequencies. Our numerical study shows a near perfect, unidirectional transmission through the skull when the NHCMM is applied while preserving the imaging information and enhancing the acoustic energy at the focal point needed for focused ultrasound used for noninvasive therapies. The proposed acoustic NHCMM lays the foundation for noninvasive ultrasonic brain imaging through an intact skull by stimulating in-vivo deep brain circuitry research and treatments for neural disorders such as brain tumors and strokes.

Influence of Transcranial Direct Current Stimulation to the Cerebellum on Standing Posture Control.

Damage to the vestibular cerebellum results in dysfunctional standing posture control. Patients with cerebellum dysfunction have a larger sway in the center of gravity while standing compared with healthy subjects. Transcranial direct current stimulation (tDCS) is a noninvasive technique for selectively exciting or inhibiting specific neural structures with potential applications in functional assessment and treatment of neural disorders. However, the specific stimulation parameters for influencing postural control have not been assessed. In this study, we investigated the influence of tDCS when applied over the cerebellum on standing posture control. Sixteen healthy subjects received tDCS (20 min, 2 mA) over the scalp 2 cm below the inion. In Experiment 1, all 16 subjects received tDCS under three stimulus conditions, Sham, Cathodal, and Anodal, in a random order with the second electrode placed on the forehead. In Experiment 2, five subjects received cathodal stimulation only with the second electrode placed over the right buccinator muscle. Center of gravity sway was measured twice for 60 s before and after tDCS in a standing posture with eyes open and legs closed, and average total locus length, locus length per second, rectangular area, and enveloped area were calculated. In Experiment 1, total locus length and locus length per second decreased significantly after cathodal stimulation but not after anodal or sham stimulation, while no tDCS condition influenced rectangular or enveloped areas. In Experiment 2, cathodal tDCS again significantly reduced total locus length and locus length per second but not rectangular and enveloped areas. The effects of tDCS on postural control are polarity-dependent, likely reflecting the selective excitation or inhibition of cerebellar Purkinje cells. Cathodal tDCS to the cerebellum of healthy subjects can alter body sway (velocity).

Implantable neurotechnologies: electrical stimulation and applications.

Neural stimulation using injected electrical charge is widely used both in functional therapies and as an experimental tool for neuroscience applications. Electrical pulses can induce excitation of targeted neural pathways that aid in the treatment of neural disorders or dysfunction of the central and peripheral nervous system. In this review, we summarize the recent trends in the field of electrical stimulation for therapeutic interventions of nervous system disorders, such as for the restoration of brain, eye, ear, spinal cord, nerve and muscle function. Neural prosthetic applications are discussed, and functional electrical stimulation parameters for treating such disorders are reviewed. Important considerations for implantable packaging and enhancing device reliability are also discussed. Neural stimulators are expected to play a profound role in implantable neural devices that treat disorders and help restore functions in injured or disabled nervous system.

Application of multiway-variate calibration to simultaneous voltammetric determination of three catecholamines.

Three structurally similar catecholamines, adrenaline (AA), dopamine (DA) and noradrenaline (NA), which are neurotransmitters well known for their treatment of neural disorders and many other diseases, were investigated at a glassy carbon electrode (GCE) with the use of differential pulse stripping voltammetry (DPSV). The aim was to develop a simple, rapid and cost effective method of simultaneous analysis of these three substances in typical samples such as human urine. Each analyte showed typical reversible redox behaviour with the use of cyclic voltammetry in aqueous medium in the pH range of 4.0-7.9, and composite voltammograms of the three analytes were found to consist of three significantly overlapping peaks corresponding to the three individual substances. Thus, two- and three-way multi-variate data analysis methods were investigated. These included unfolding methods such as-partial least squares (UPLS), principal component regression (UPCR) and radial basis function-artificial neural networks (URBF-ANN), as well as trilinear models, such as parallel factor analysis (PARAFAC) and N-way PLS (NPLS). The results were compared with those obtained from two-way voltammetric data matrix with the use of conventional models, PLS, PCR and RBF-ANN. It was found that most of the three-way models, such as PARAFAC and UPLS, performed somewhat better than others on the basis of the %RPET (5.6∼5.9) and mean %Recovery (94∼102). The proposed methods were then applied for the determination of human urine samples spiked with the three catecholamines, and the results were satisfactory.

Methylacridinium and its Cholinergic Properties

10-Methylacridinium iodide (methylacridinium; MA) is an inhibitor of cholinesterases. Inhibitors of acetylcholinesterase (AChE) are used in the treatment of myasthenia gravis, Alzheimer's disease, and in the prophylaxis of poisoning with organophosphates. Using spectrophotometric Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50) = 1.68 +/- 0.14 1M; human recombinant AChE) and equally to its inhibition of butyrylcholinesterase (BuChE; IC(50) = 3.54 +/- 0.27 1M; BuChE from human serum). MA also inhibits the binding of [(3)H]N-methylscopolamine to the muscarinic M2 receptor subtype, possibly in an allosteric manner (IC(50) = 1.90 1M). Functional effects on both the enzyme and the receptor could be observed in contractile studies on the isolated rat bladder. The ability of MA to cross the blood-brain barrier (log P = -0.32; polar surface area 3.88) provides prerequisites for a potential use of the drug in the treatment of neural disorders.