Engineered Regenerative Isolated Peripheral Nerve Interface for Targeted Reinnervation.

A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation. In this in vivo study, after over 8 months of RPNI surgery, the eRIPEN exhibits a minimum Feret diameter of 15-20 µm with a cross-sectional area of 100-500 µm2, representing the largest distribution of myofibers. Furthermore, neuromuscular junction formation and muscle contraction with a force of ≈28 N are observed. Notably, the decreased hypersensitivity to mechanical/thermal stimuli and an improved tibial functional index from -77 to -56 are found in the eRIPEN group. The present novel concept of eRIPEN paves the way for the utilization and application of tissue-engineered constructs in RPNI, ultimately realizing neuroprosthesis control through synaptic connections.

Digital Phenotyping of Geriatric Depression Using a Community-Based Digital Mental Health Monitoring Platform for Socially Vulnerable Older Adults and Their Community Caregivers: 6-Week Living Lab Single-Arm Pilot Study.

BACKGROUND: Despite the increasing need for digital services to support geriatric mental health, the development and implementation of digital mental health care systems for older adults have been hindered by a lack of studies involving socially vulnerable older adult users and their caregivers in natural living environments. OBJECTIVE: This study aims to determine whether digital sensing data on heart rate variability, sleep quality, and physical activity can predict same-day or next-day depressive symptoms among socially vulnerable older adults in their everyday living environments. In addition, this study tested the feasibility of a digital mental health monitoring platform designed to inform older adult users and their community caregivers about day-to-day changes in the health status of older adults. METHODS: A single-arm, nonrandomized living lab pilot study was conducted with socially vulnerable older adults (n=25), their community caregivers (n=16), and a managerial social worker over a 6-week period during and after the COVID-19 pandemic. Depressive symptoms were assessed daily using the 9-item Patient Health Questionnaire via scripted verbal conversations with a mobile chatbot. Digital biomarkers for depression, including heart rate variability, sleep, and physical activity, were measured using a wearable sensor (Fitbit Sense) that was worn continuously, except during charging times. Daily individualized feedback, using traffic signal signs, on the health status of older adult users regarding stress, sleep, physical activity, and health emergency status was displayed on a mobile app for the users and on a web application for their community caregivers. Multilevel modeling was used to examine whether the digital biomarkers predicted same-day or next-day depressive symptoms. Study staff conducted pre- and postsurveys in person at the homes of older adult users to monitor changes in depressive symptoms, sleep quality, and system usability. RESULTS: Among the 31 older adult participants, 25 provided data for the living lab and 24 provided data for the pre-post test analysis. The multilevel modeling results showed that increases in daily sleep fragmentation (P=.003) and sleep efficiency (P=.001) compared with one's average were associated with an increased risk of daily depressive symptoms in older adults. The pre-post test results indicated improvements in depressive symptoms (P=.048) and sleep quality (P=.02), but not in the system usability (P=.18). CONCLUSIONS: The findings suggest that wearable sensors assessing sleep quality may be utilized to predict daily fluctuations in depressive symptoms among socially vulnerable older adults. The results also imply that receiving individualized health feedback and sharing it with community caregivers may help improve the mental health of older adults. However, additional in-person training may be necessary to enhance usability. TRIAL REGISTRATION: ClinicalTrials.gov NCT06270121; https://clinicaltrials.gov/study/NCT06270121.

Insular cortex stimulation alleviates neuropathic pain through changes in the expression of collapsin response mediator protein 2 involved in synaptic plasticity.

In recent studies, brain stimulation has shown promising potential to alleviate chronic pain. Although studies have shown that stimulation of pain-related brain regions can induce pain-relieving effects, few studies have elucidated the mechanisms of brain stimulation in the insular cortex (IC). The present study was conducted to explore the changes in characteristic molecules involved in pain modulation mechanisms and to identify the changes in synaptic plasticity after IC stimulation (ICS). Following ICS, pain-relieving behaviors and changes in proteomics were explored. Neuronal activity in the IC after ICS was observed by optical imaging. Western blotting was used to validate the proteomics data and identify the changes in the expression of glutamatergic receptors associated with synaptic plasticity. Experimental results showed that ICS effectively relieved mechanical allodynia, and proteomics identified specific changes in collapsin response mediator protein 2 (CRMP2). Neuronal activity in the neuropathic rats was significantly decreased after ICS. Neuropathic rats showed increased expression levels of phosphorylated CRMP2, alpha amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR), and N-methyl-d-aspartate receptor (NMDAR) subunit 2B (NR2B), which were inhibited by ICS. These results indicate that ICS regulates the synaptic plasticity of ICS through pCRMP2, together with AMPAR and NR2B, to induce pain relief.

Fork-shaped neural interface with multichannel high spatial selectivity in the peripheral nerve of a rat.

Objective.This study aims to develop and validate a sophisticated fork-shaped neural interface (FNI) designed for peripheral nerves, focusing on achieving high spatial resolution, functional selectivity, and improved charge storage capacities. The objective is to create a neurointerface capable of precise neuroanatomical analysis, neural signal recording, and stimulation.Approach.Our approach involves the design and implementation of the FNI, which integrates 32 multichannel working electrodes featuring enhanced charge storage capacities and low impedance. An insertion guide holder is incorporated to refine neuronal selectivity. The study employs meticulous electrode placement, bipolar electrical stimulation, and comprehensive analysis of induced neural responses to verify the FNI's capabilities. Stability over an eight-week period is a crucial aspect, ensuring the reliability and durability of the neural interface.Main results.The FNI demonstrated remarkable efficacy in neuroanatomical analysis, exhibiting accurate positioning of motor nerves and successfully inducing various movements. Stable impedance values were maintained over the eight-week period, affirming the durability of the FNI. Additionally, the neural interface proved effective in recording sensory signals from different hind limb areas. The advanced charge storage capacities and low impedance contribute to the FNI's robust performance, establishing its potential for prolonged use.Significance.This research represents a significant advancement in neural interface technology, offering a versatile tool with broad applications in neuroscience and neuroengineering. The FNI's ability to capture both motor and sensory neural activity positions it as a comprehensive solution for neuroanatomical studies. Moreover, the precise neuromodulation potential of the FNI holds promise for applications in advanced bionic prosthetic control and therapeutic interventions. The study's findings contribute to the evolving field of neuroengineering, paving the way for enhanced understanding and manipulation of peripheral neural functions.

Associations Between Psychological Stress and Hand Pain Among Rural and Urban Adults: Findings From the KoGES Community Cohort Study.

Despite known health disparities in chronic pain conditions between rural and urban adults, few studies have examined whether longitudinal associations between psychological stress and hand pain differ. Utilizing community-based cohort data, this study examined whether rural and urban adults differed in the extent to which psychological distress was associated with hand osteoarthritis (OA) symptoms and later functional limitations related to hand pain. Community-dwelling adults (mean age = 51.97, 52.3% women) in a rural (n = 2,971) and urban area (n = 2,782) provided demographic data at baseline and, at a 4-year follow-up, responded to questionnaires about psychological distress and clinical symptoms of hand OA. Levels of functional limitations in hands were assessed at an 8-year follow-up. Ordinal logistic and linear regression were conducted to examine the effects of psychological distress on hand OA symptoms and functional limitations, and whether associations between psychological distress and these pain outcomes were moderated by residential area. The results showed that psychological distress was associated with a higher risk for hand OA symptoms and functional limitations, even after adjusting for demographic and health covariates. There was significant moderation by residential area, such that the association between psychological distress and hand OA was significant only among rural adults and the association with functional limitations was stronger in rural adults than urban adults. Findings suggest greater vulnerability to hand arthritis and hand-related functional limitations among rural adults and the potential for tailored intervention programs to help resolve health disparities among rural communities. PERSPECTIVE: This study compares the association between psychological distress and hand pain outcomes between rural and urban adults using community-based cohort data and suggests that rural adults are more vulnerable to experiencing negative effects of psychological distress on concurrent hand OA symptoms and longitudinal functional limitations in hands.

Protection of the Vascular System by Polyethylene Glycol Reduces Secondary Injury Following Spinal Cord Injury in Rats.

BACKGROUND: Polyethylene glycol (PEG) is a hydrophilic polymer, which has been known to have a neuroprotective effect by sealing the ruptured cell membrane, but PEG effects on the vascular systems and its underlying mechanisms remain unclear. Here, we showed the neuroprotective effect of PEG by preventing damage to the vascular system. METHODS: A spinal contusion was made at the T11 segment in male Sprague-Dawley rats. PEG was injected into the subdural space immediately after SCI. Vascular permeability was assessed for 24 h after SCI using intraperitoneally injected Evans blue dye. Junctional complexes were stained with CD31 and ZO-1. Infarct size was analyzed using triphenyltetrazolium chloride, and blood vessels were counted in the epicenter. Behavioral tests for motor and sensory function were performed for 6 weeks. And then the tissue-sparing area was assessed. RESULTS: Immediately applied PEG significantly reduced the vascular permeability at 6, 12, and 24 h after SCI when it compared to saline, and infarct size was also reduced at 0, 6, and 24 h after SCI. In addition, a great number of blood vessels were observed in PEG group at 6 and 24 h after SCI compared to those of the saline group. The PEG group also showed a significant improvement in motor function. And tissue-sparing areas in the PEG were greater than those of the saline group. CONCLUSION: The present results provide preclinical evidence for the neuroprotective effects of PEG as a promising therapeutic agent for reducing secondary injury following SCI through vascular protection.

Fully Implantable Neurostimulation System for Long-Term Behavioral Animal Study.

Spinal cord stimulation (SCS) is an emerging therapeutic option for patients with neuropathic pain due to spinal cord injury (SCI). Numerous studies on pain relief effects with SCS have been conducted and demonstrated promising results while the mechanisms of analgesic effect during SCS remain unclear. However, an experimental system that enables large-scale long-term animal studies is still an unmet need for those mechanistic studies. This study proposed a fully wireless neurostimulation system that can efficiently support a long-term animal study for neuropathic pain relief. The developed system consists of an implantable stimulator, an animal cage with an external charging coil, and a wireless communication interface. The proposed device has the feature of remotely controlling stimulation parameters via radio-frequency (RF) communication and wirelessly charging via magnetic induction in freely moving rats. Users can program stimulation parameters such as pulse width, intensity, and duration through an interface on a computer. The stimulator was packaged with biocompatible epoxy to ensure long-term durability under in vivo conditions. Animal experiments using SCI rats were conducted to demonstrate the functionality of the device, including long-term usability and therapeutic effects. The developed system can be tailored to individual user needs with commercially available components, thus providing a cost-effective solution for large-scale long-term animal studies on neuropathic pain relief.

Pathological Characteristics of Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

BACKGROUND: This study aimed to identify pain-related behavior and pathological characteristics of the knee joint in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA). METHODS: Knee joint inflammation was induced by intra-articular injection of MIA (4 mg/50 µL, n = 14) in 6-week-old male rats. Knee joint diameter, weight-bearing percentage on the hind limb during walking, the knee bending score, and paw withdrawal to mechanical stimuli were measured to evaluate edema and pain-related behavior for 28 d after MIA injection. Histological changes in the knee joints were evaluated using safranin O fast green staining on days 1, 3, 5, 7, 14, and 28 after OA induction (n = 3, respectively). Changes in bone structure and bone mineral density (BMD) were examined 14 and 28 d after OA (n = 3, respectively) using micro-computed tomography (CT). RESULTS: The knee joint diameter and knee bending scores of the ipsilateral joint significantly increased 1 d after MIA injection, and the increased knee joint diameter and knee bending score persisted for 28 d. Weight-bearing during walking and paw withdrawal threshold (PWT) decreased from 1 and 5 d, respectively, and were maintained up to 28 d after MIA. Cartilage destruction started on day 1, and Mankin scores for bone destruction significantly increased for 14 d, as shown by micro-CT imaging. CONCLUSION: The present study demonstrated that histopathological structural changes in the knee joint due to inflammation started soon after MIA injection, which induced OA pain from inflammation-related acute pain to spontaneous and evoked associated chronic pain.

Video augmented mirror therapy for upper extremity rehabilitation after stroke: a randomized controlled trial.

PURPOSE: To investigate the effects of mirror therapy using a newly developed video augmented wearable reflection device on reach-to-grasp motor control and upper extremity motor function. METHODS: Participants were randomly allocated to one of three groups: mirror therapy using a video augmented wearable reflection device group (MTVADG), n = 12; traditional mirror therapy group (TMTG), n = 12; and control group (CG), n = 12. Participants in the MTVADG and TMTG received conventional rehabilitation in addition to mirror therapy. Motor control during the reach-to-grasp movement was assessed using kinematic analysis. Each participant's upper extremity motor function was assessed using the Fugl-Meyer Assessment, Manual Function Test, and Box and Block Test. RESULTS: While both the MTVADG and TMTG showed significantly improved reach-to-grasp movement. The MTVADG showed greater efficiency in kinematic performance than the TMTG. Moreover, while both the MTVADG and TMTG showed improved upper extremity motor function, the MTVADG showed significantly greater improvement in proximal upper limb function compared to the TMTG. CONCLUSION: Our results suggested that mirror therapy using a video augmented wearable reflection device is more efficient compared to traditional mirror therapy for patients with stroke. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER: KCT0003047.

Agreement between Azure Kinect and Marker-Based Motion Analysis during Functional Movements: A Feasibility Study.

(1) Background: The present study investigated the agreement between the Azure Kinect and marker-based motion analysis during functional movements. (2) Methods: Twelve healthy adults participated in this study and performed a total of six different tasks including front view squat, side view squat, forward reach, lateral reach, front view lunge, and side view lunge. Movement data were collected using an Azure Kinect and 12 infrared cameras while the participants performed the movements. The comparability between marker-based motion analysis and Azure Kinect was visualized using Bland-Altman plots and scatter plots. (3) Results: During the front view of squat motions, hip and knee joint angles showed moderate and high level of concurrent validity, respectively. The side view of squat motions showed moderate to good in the visible hip joint angles, whereas hidden hip joint angle showed poor concurrent validity. The knee joint angles showed variation between excellent and moderate concurrent validity depending on the visibility. The forward reach motions showed moderate concurrent validity for both shoulder angles, whereas the lateral reach motions showed excellent concurrent validity. During the front view of lunge motions, both the hip and knee joint angles showed moderate concurrent validity. The side view of lunge motions showed variations in concurrent validity, while the right hip joint angle showed good concurrent validity; the left hip joint showed poor concurrent validity. (4) Conclusions: The overall agreement between the Azure Kinect and marker-based motion analysis system was moderate to good when the body segments were visible to the Azure Kinect, yet the accuracy of tracking hidden body parts is still a concern.

Analgesic Tolerance Development during Repetitive Electric Stimulations Is Associated with Changes in the Expression of Activated Microglia in Rats with Osteoarthritis.

Electric stimulation is used for managing osteoarthritic (OA) pain; however, little is known about the development of analgesic tolerance during repeated stimulations and the relation of spinal microglia with OA pain. We investigated the changes in the analgesic effects of repeated electric stimulations and the relation between the development of analgesic tolerance and spinal microglial expression in rats with OA. To induce OA, monosodium iodoacetate was injected into the synovial space of the right knee joint of the rats (n = 185). Repeated high frequency, low frequency, or sham transcutaneous electric nerve stimulation (TENS) was performed to the ipsilateral knee joint for 20 min in rats with OA (n = 45). Minocycline or minocycline plus TENS (HF, LF, or sham) was treated in OA rats with repeated TENS-induced tolerance (n = 135). Immunohistochemistry of the microglia in the L3-L5 spinal segments was performed. Knee joint pain during passive movement of the knee joint were quantified using the knee-bend score and the proportion of activated microglia was calculated as primary variables. Paw withdrawal threshold (hypersensitivity to mechanical stimuli) was assessed and the resting and activated microglia were counted as secondary variables. Repeated applications decreased the analgesic effect of TENS on OA pain and failed to reduce the expression of activated microglia in the spinal cord. However, spinal microglial inhibition by minocycline restored the analgesic effect of TENS on OA pain in TENS-tolerant OA rats. TENS combined with minocycline treatment improved knee joint pain and mechanical hypersensitivity in TENS-tolerant OA rats, and inhibited the expression of activated microglia in the spinal cord. These results suggest a possible relationship between repetitive electric stimulation-induced analgesic tolerance for OA pain control and changes in microglia activation.

Hydrogel-Assisted Electrospinning for Fabrication of a 3D Complex Tailored Nanofiber Macrostructure.

Electrospinning has shown great potential in tissue engineering and regenerative medicine due to a high surface-area-to-volume ratio and an extracellular matrix-mimicking structure of electrospun nanofibers, but the fabrication of a complex three-dimensional (3D) macroscopic configuration with electrospun nanofibers remains challenging. In the present study, we developed a novel hydrogel-assisted electrospinning process (GelES) to fabricate a 3D nanofiber macrostructure with a 3D complex but tailored configuration by utilizing a 3D hydrogel structure as a grounded collector instead of a metal collector in conventional electrospinning. The 3D hydrogel collector was discovered to effectively concentrate the electric field toward itself similar to the metal collector, thereby depositing electrospun nanofibers directly on its exterior surface. Synergistic advantages of the hydrogel (e.g., biocompatibility and thermally reversible sol-gel transition) and the 3D nanofiber macrostructure (e.g., mechanical robustness and high permeability) provided by the GelES process were demonstrated in a highly permeable tubular tissue graft and a robust drug- or cell-encapsulation construct. GelES is expected to broaden potential applications of electrospinning to not only provide in vivo drug/cell delivery and tissue regeneration but also an in vitro drug testing platform by increasing the degree of freedom in the configuration of the 3D nanofiber macrostructure.

Effect of core materials for core fabrication for dental implants on in-vitro cytocompatibility of MC3T3-E1 cells.

BACKGROUND: Despite the wide use of dental materials for CAD/CAM system in prosthetic treatment, the effect of the materials, which are used as dental implants core fabricated, on cells involved in dental implant osseointegration is uncertain. This study aimed to investigate and compare the effect of single core materials used for dental implants fabricated by the dental prostheses fabrication process and the CAD/CAM milling method on MC3T3-E1 cells. METHODS: The materials used for prostheses restoration in this experiment were Porcelain Fused Gold (P.F.G), Lithium disilicate glass ceramic (LiSi2), Zirconia (ZrO2), Nickel-Chromium (Ni-Cr) and Cobalt-Chromium (Co-Cr). MC3T3-E1 cells were cultured and used, the cell adhesion and morphology were observed and analyzed using confocal laser scanning microscopy (CLSM). Methoxyphenyl tetrazolium salt (MTS) and alkaline phosphatase (ALP) assay were used to observe the cell proliferation and differentiation. RESULTS: CLSM revealed irregular cell adhesion and morphology and the filopodia did not spread in the Ni-Cr specimen group. Significantly high cell proliferation was observed in the ZrO2 specimen group. The LiSi2 specimen group presented significantly high cell differentiation. Intergroup comparison of cell proliferation and differentiation between the Ni-Cr specimen group and all other specimen groups showed significant differences (p < .05). CONCLUSION: Cell proliferation and differentiation were observed from the cores, which were fabricated with all specimen groups on cytocompatibility except the Ni-Cr specimen group.

Transcutaneous Electrical Nerve Stimulation Reduces Knee Osteoarthritic Pain by Inhibiting Spinal Glial Cells in Rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain control. However, the effects of TENS on osteoarthritis (OA) pain and potential underlying mechanisms remain unclear. OBJECTIVE: The objective of this study was to investigate the effect of TENS on OA pain treatment and underlying mechanisms related to glial cell inhibition. DESIGN: This was an experimental study. METHODS: OA was induced by injection of monosodium iodoacetate into the synovial space of the right knee joint of rats. High-frequency (HF) TENS (100 Hz), low-frequency (LF) TENS (4 Hz), or sham TENS was applied to the ipsilateral knee joint for 20 minutes. Paw withdrawal threshold (PWT), weight bearing, and knee bend score (KBS) were measured. Immunohistochemistry for microglia and astrocytes was performed with L3 to L5 spinal segment samples. To investigate the effects of glial inhibition on OA pain, minocycline, l-α-aminoadipate, or artificial cerebrospinal fluid was injected intrathecally, and PWT and KBS were measured. RESULTS: Compared with sham TENS, both HF TENS and LF TENS significantly increased PWT, decreased KBS, and inhibited activated microglia in the L3 to L5 segments but did not decrease the total number of microglia, except in the L4 segment (HF TENS). Astrocyte expression was significantly decreased in the L3 to L5 segments following LF TENS and in the L3 segment following HF TENS. Compared with artificial cerebrospinal fluid, both minocycline and l-α-aminoadipate increased PWT and decreased KBS. LIMITATIONS: These results cannot be generalized to humans. CONCLUSIONS: TENS alleviates OA pain in rats by inhibiting activated microglia and reducing astrocyte expression in the spinal cord. Although these results may not be generalizable to chronic pain in patients with OA, within the limitation of the experimental animal model used in the present study, they suggest a possible mechanism and preclinical evidence supporting further experimentation or clinical use of TENS in humans.

Alterations in protein expression patterns of spinal peroxisome proliferator-activated receptors after spinal cord injury.

Objectives: Peroxisome proliferator-activated receptors (PPARs) control wound healing processes in damaged tissues. PPAR agonists have neuroprotective effects in spinal cord injury (SCI); however, isotype-specific roles of PPARs are not well understood. Therefore, we evaluated protein expression changes for three isotypes of PPARs at different time points and locations relative to the epicenter after SCI in rats. Methods: A 10-g rod was dropped on the spinal cord which located at the T10 vertebra of rats from a height of 6.25, 12.5, or 50 mm using New York University impactor. We collected the spinal cord at 6, 12, 24, and 72 h and 1, 3, and 5 weeks after SCI. The protein expression of PPARs was analyzed using western blot. Results: The protein expression of PPAR-α declined gradually up to 5 weeks at the epicenter. PPAR-ß/δ expression increased from 3 days to 5 weeks at the caudal region, but decreased at the epicenter in the severe injury group. PPAR-γ expression increased significantly at all regions in all three injury groups up to 5 weeks after SCI and increased to a greater extent in the severe injury group. In addition, PPAR-ß/δ controlled protein expression of PPAR-α positively, and -γ negatively. Conclusions: The present results suggest that different PPAR isotypes have varied protein expression patterns at the epicenter and in adjacent regions after SCI. Our results suggest that PPARs may have overlapping but distinct roles. These findings will be useful for further studies investigating PPARs in neurological disorders including SCI.

Effect of stretching-based rehabilitation on pain, flexibility and muscle strength in dancers with hamstring injury: a single-blind, prospective, randomized clinical trial.

BACKGROUND: Hamstring injuries commonly occur in mainstream sports and occupations that involve physical activity. We evaluated the effect of a stretching-based rehabilitation program on pain, flexibility, and strength in dancers with hamstring injuries. METHODS: Sixteen Korean traditional dancers with unilateral hamstring injuries were included and randomly assigned to a rehabilitation or control group. The rehabilitation group received stretching-based rehabilitation for 8 weeks, which comprised simple static stretches and basic range of motion (ROM) exercises, such as static and active stretching, concentric and eccentric ROM training, and trunk stabilization exercises. The control group received conventional treatment with analgesics and physical therapy. Outcomes were assessed before and after the interventions in both groups by comparing the Visual Analog Scale (VAS) score for pain, straight leg raise ROM Test for hamstring muscle flexibility, and isometric strength test for hamstring muscle strength. RESULTS: Subjects who underwent rehabilitation showed significant improvements in VAS score for pain (P=0.017) and ROM for flexibility (P<0.001). Muscle strength also increased after the rehabilitation program (P<0.05). CONCLUSIONS: This rehabilitation program effectively decreases pain and increases flexibility and strength in patients with hamstring injury. The data indicate that a stretching-based rehabilitation program can help promote functional recovery from hamstring injury.

Whole-Body Vibration Combined with Treadmill Training Improves Walking Performance in Post-Stroke Patients: A Randomized Controlled Trial.

BACKGROUND Stroke is characterized by an asymmetrical gait pattern that causes poor stability and reduces overall activity levels. The aim of this study was to investigate the effect of whole-body vibration combined with treadmill training (WBV-TT) on walking performance in patients with chronic stroke. MATERIAL AND METHODS Thirty ambulatory chronic stroke patients were randomly allocated to the WBV-TT group or the treadmill training (TT) group. The participants in the WBV-TT group performed 6 types of exercises on a vibrating platform for 4.5 minutes and then walked on the treadmill for 20 minutes. The participants in the TT group conducted the same exercise on a platform without vibration and then walked on the treadmill in the same manner. The vibration lasted for 45 seconds in each exercise, and the intervention was performed 3 times weekly for 6 weeks. The treadmill walking speed was gradually increased by 5% in both groups. The outcome measures included the temporospatial parameter of gait (GAITRite®) and 6-minute walk test. RESULTS The WBV-TT group showed significant improvements in walking performance with respect to walking speed, cadence, step length, stride length, single-limb support, double-limb support, and 6-minute walk test compared with baseline (p<0.05). Significant improvements were also seen in walking speed, step length, stride length, and double-limb support compared with the TT group (p<0.05). CONCLUSIONS These findings indicate that WBV-TT is more effective than TT for improving walking performance of patients with chronic stroke.

Low-Level Laser Irradiation Improves Motor Recovery After Contusive Spinal Cord Injury in Rats.

This study investigated the therapeutic effects of low-level laser irradiation (LLLI) on the recovery of motor function and its underlying mechanisms in rats with spinal cord injury (SCI). The spinal cord was contused at the T11 level using a New York University impactor. Thirty-eight rats were randomly divided into four groups: LLLI with 0.08 J, 0.4 J, 0.8 J, and sham. We transcutaneously applied at the lesion site of the spinal contusive rats 5 min after injury and then daily for 21 days. The Basso, Beattie and Bresnahan (BBB) locomotor scale and combined behavioral score (CBS) were used to evaluate motor function. The spinal segments of rostral and caudal from the lesion site, the epicenter, and L4-5 were collected from normal and the all groups at 7 days after SCI. The expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) was compared across groups in all regions. In the present study, LLLI with 0.4 J and 0.8 J led to a significant improvement in motor function compared to sham LLLI, which significantly decreased TNF-α expression at the lesion epicenter and reduced iNOS expression in the caudal segment for all LLLI groups and in the L4-5 segments for the 0.4 J and 0.8 J groups when compared to sham LLLI group. Our results demonstrate that transcutaneous LLLI modulate inflammatory mediators to enhance motor function recovery after SCI. Thus, LLLI in acute phase after SCI might have therapeutic potential for neuroprotection and restoration of motor function following SCI.

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats.

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 µl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Intrathecal Transplantation of Embryonic Stem Cell-Derived Spinal GABAergic Neural Precursor Cells Attenuates Neuropathic Pain in a Spinal Cord Injury Rat Model.

Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell-derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons. Interestingly, low doses of SHH and RA induced MGE-like progenitors, which expressed low levels of DARPP32 and Nkx2.1 and high levels of Irx3 and Pax6. These cells subsequently generated the majority of the DARPP32(-) GABAergic neurons after in vitro differentiation. The spinal mESC-NPCs were intrathecally transplanted into the lesion area of the spinal cord around T10-T11 at 21 days after SCI. The engrafted spinal GABAergic neurons remarkably increased both the paw withdrawal threshold (PWT) below the level of the lesion and the vocalization threshold (VT) to the level of the lesion (T12, T11, and T10 vertebrae), which indicates attenuation of chronic neuropathic pain by the spinal GABAergic neurons. The transplanted cells were positive for GABA antibody staining in the injured region, and cells migrated to the injured spinal site and survived for more than 7 weeks in L4-L5. The mESC-NPC-derived spinal GABAergic neurons dramatically attenuated the chronic neuropathic pain following SCI, suggesting that the spinal GABAergic mESC-NPCs cultured with low doses of SHH and RA could be alternative cell sources for treatment of SCI neuropathic pain by stem cell-based therapies.