Optogenetic neuronal stimulation promotes axon outgrowth and myelination of motor neurons in a three-dimensional motor neuron-Schwann cell coculture model on a microfluidic biochip.

Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron-Schwann cell (MN-SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs.

Dedifferentiated Schwann cells secrete progranulin that enhances the survival and axon growth of motor neurons.

Schwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon regrowth of damaged neurons, but the identities of neurotrophic factors remain incompletely understood. Here we show that SCs express and secrete progranulin (PGRN), depending on the differentiation status of SCs.

Primary Motor Neuron Culture to Promote Cellular Viability and Myelination.

A culture system that can recapitulate myelination in vitro will not only help us to better understand the mechanism of myelination and demyelination but also identify possible therapeutic interventions for treating demyelinating diseases. Here, we introduce a simple and reproducible myelination culture system using mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are plated on a feeder layer of SCs, which interact with and wrap around the axons of MNs as they differentiate in culture.

Cubic-phase zirconia nano-island growth using atomic layer deposition and application in low-power charge-trapping nonvolatile-memory devices.

The manipulation of matter at the nanoscale enables the generation of properties in a material that would otherwise be challenging or impossible to realize in the bulk state. Here, we demonstrate growth of zirconia nano-islands using atomic layer deposition on different substrate terminations. Transmission electron microscopy and Raman measurements indicate that the nano-islands consist of nano-crystallites of the cubic-crystalline phase, which results in a higher dielectric constant (κ ∼ 35) than the amorphous phase case (κ ∼ 20).

Investigation of the Changes in Electronic Properties of Nickel Oxide (NiO) Due to UV/Ozone Treatment.

Drastic reduction in nickel oxide (NiO) film resistivity and ionization potential is observed when subjected to ultraviolet (UV)/ozone (O) treatment. X-ray photoemission spectroscopy suggests that UV/O treatment changes the film stoichiometry by introducing Ni vacancy defects. Oxygen-rich NiO having Ni vacancy defects behaves as a p-type semiconductor.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction.

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE-induced overactive contraction.

Engineering three dimensional micro nerve tissue using postnatal stem cells from human dental apical papilla.

The in vitro generation of cell-based three dimensional (3D) nerve tissue is an attractive subject to improve graft survival and integration into host tissue for neural tissue regeneration or to model biological events in stem cell differentiation. Although 3D organotypic culture strategies are well established for 3D nerve tissue formation of pluripotent stem cells to study underlying biology in nerve development, cell-based nerve tissues have not been developed using human postnatal stem cells with therapeutic potential. Here, we established a culture strategy for the generation of in vitro cell-based 3D nerve tissue from postnatal stem cells from apical papilla (SCAPs) of teeth, which originate from neural crest-derived ectomesenchyme cells.

Optogenetic Inhibition of the Subthalamic Nucleus Reduces Levodopa-Induced Dyskinesias in a Rat Model of Parkinson's Disease.

Background: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the amelioration of levodopa-induced dyskinesia. However, electrical deep brain stimulation cannot specifically activate or inactivate selected types of neurons.

Objectives: We applied optogenetics as an alternative treatment to deep brain stimulation for levodopa-induced dyskinesia, and also to confirm that the mechanism of levodopa-induced dyskinesia amelioration by subthalamic nucleus deep brain stimulation is mediated through neuronal inhibition.

Characteristics of the neuronal firing patterns in the subthalamic nucleus with graded dopaminergic cell loss in the nigrostriatal pathway.

The aim of this study was to evaluate the neuronal firing changes in the subthalamic nucleus (STN) in a graded mouse model of Parkinson's disease. Unilateral graded dopaminergic cell loss in the substantia nigra pars compacta was achieved by injecting different concentrations of 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle. Electrophysiological analysis of neuronal firing patterns in the STN revealed an increased firing rate, burst index, and interspike interval coefficient of variation in groups treated with higher 6-OHDA concentrations.

An implantable wireless optogenetic stimulation system for peripheral nerve control.

An implantable wireless optogenetic stimulation system with an LED-based optical stimulation cuff electrode was developed for peripheral nerve control. The proposed system consisted of a battery-powered optical cuff electrode, optical stimulation controller, and wireless communication system. The optical cuff electrode had a polydimethylsiloxane (PDMS) structure was designed to illuminate the entire sciatic nerve.

A time-course study of behavioral and electrophysiological characteristics in a mouse model of different stages of Parkinson's disease using 6-hydroxydopamine.

Parkinson's disease (PD) is characterized by abnormal motor symptoms and increased neuronal activity in the subthalamic nucleus (STN) as the disease progresses. We investigated the behavioral and electrophysiological characteristics in a mouse model mimicking the progressive stages of human PD (early, moderate, and advanced) by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB) at three different concentrations (2, 4, and 6 μg/2 μl). Significant changes in motor symptoms were demonstrated between groups in association with relative TH-positive cell loss in the substantia nigra pars compacta (SNc).

Enhanced efficacy of human brain-derived neural stem cells by transplantation of cell aggregates in a rat model of Parkinson's disease.

Objective: Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons.

Optogenetic inactivation of the subthalamic nucleus improves forelimb akinesia in a rat model of Parkinson disease.

Background: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the therapeutic effects in patients with Parkinson disease (PD) but cannot specifically activate or inactivate different types of neurons. Recently, a new technology based on optogenetics has been developed to modulate the activity of specific neurons. However, the therapeutic effects of optical inactivation in the subthalamic nucleus (STN) have not been fully investigated.

Feedback control of electrode offset voltage during functional electrical stimulation.

Control of the electrode offset voltage is an important issue related to the processes of functional electrical stimulation because excess charge accumulation over time damages both the tissue and the electrodes. This paper proposes a new feedback control scheme to regulate the electrode offset voltage to a predetermined reference value. The electrode offset voltage was continuously monitored using a sample-and-hold (S/H) circuit during stimulation and non-stimulation periods.

Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum.

Gait phase detection from sciatic nerve recordings in functional electrical stimulation systems for foot drop correction.

Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers.

Improvement of wireless power transmission efficiency of implantable subcutaneous devices by closed magnetic circuit mechanism.

Induction coils were fabricated based on flexible printed circuit board for inductive transcutaneous power transmission. The coil had closed magnetic circuit (CMC) structure consisting of inner and outer magnetic core. The power transmission efficiency of the fabricated device was measured in the air and in vivo condition.

Improvement of signal-to-interference ratio and signal-to-noise ratio in nerve cuff electrode systems.

Cuff electrodes are effective for chronic electroneurogram (ENG) recording while minimizing nerve damage. However, the ENG signals are usually contaminated by electromyogram (EMG) activity from the surrounding muscles, stimulus artifacts produced by the electrical stimulation and noise generated in the first stage of the neural signal amplifier. This paper proposed a new cuff electrode to reduce the interference from EMG signals and stimulus artifacts.

Spontaneous synchronized burst firing of subthalamic nucleus neurons in rat brain slices measured on multi-electrode arrays.

The current study presents an organotypic rat midbrain slice culture that served as a consistent and informative framework, where the STN neurons and their interconnectivity were closely examined with respect to electrophysiological and pharmacological properties. From multi-electrode array recordings, it was found that the majority of STN neurons spontaneously fired in bursts rather than tonically under control conditions, and the neural activity between pairs of burst-firing STN neurons was tightly correlated. This spontaneous synchronized burst firing was also affected by a glutamate receptor antagonist, yet unaffected by a GABA receptor antagonist.

The first neural probe integrated with light source (blue laser diode) for optical stimulation and electrical recording.

In this paper, we report a neural probe which can selectively stimulate target neurons optically through Si wet etched mirror surface and record extracellular neural signals in iridium oxide tetrodes. Consequently, the proposed approach provides to improve directional problem and achieve at least 150/m gap distance between stimulation and recording sites by wet etched mirror surface in V-groove. Also, we developed light source, blue laser diode (OSRAM Blue Laser Diode_PL 450), integration through simple jig for one-touch butt-coupling.

Effects of storage time on the mechanical properties of rabbit peripapillary sclera after enucleation.

In the field of biomechanics, little research has been performed to evaluate the effect of storage time on the material properties of ocular tissues. Twenty-four rabbit eyes were divided into six groups with storage times from 3 to 72 hr. A tensile specimen was prepared from the inferior quadrant of each sclera and was subjected to a stress relaxation test.

Differential phenotypic characteristics of heterogeneous cell population in the rabbit periosteum.

Background: Periosteum and periosteum-derived progenitor cells have demonstrated the potential for stimulative applications in repair of various musculoskeletal tissues. It has been found that the periosteum contains mesenchymal progenitor cells that are capable of differentiating into either osteoblasts or chondrocytes, depending on the culture conditions. Anatomically, the periosteum is a heterogeneous multilayered membrane, consisting of an outer fibrous and an inner cambium layer.

Biphasic poroviscoelastic characteristics of proteoglycan-depleted articular cartilage: simulation of degeneration.

This study investigated the biphasic poroviscoelastic properties of normal and proteoglycan-depleted articular cartilage to validate this model for use in the diagnosis of degenerated cartilage. A normal control group, a buffer-treated control group, and a trypsin-treated proteoglycan-depleted experimental group were investigated. Water content and glycosaminoglycan concentration were measured for each group in order to assess the affects of buffer treatment and trypsin treatment on normal articular cartilage.