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To explore the efficacy and possible mechanisms of Low-intensity focused ultrasound (LIFU) in alleviating spasticity caused by Spinal cord injury (SCI).We selected male Sprague-Dawley rats as subjects and performed transverse injuries on the T9 vertebra of their spinal cord (SC) to build SCI. On the 7th day after SCI, LIFU treatment was performed below the SCI segment once a day for 20 min, for 4 consecutive weeks. During treatment, a pressure sensor was used to assess the degree of spasticity. After treatment, the SC tissues from the treatment sites of the SCI+LIFU(-) and SCI+LIFU(+) groups were extracted, and high-throughput sequencing was performed to identify the changes in proteomics. In addition, expression of the growth associated protein 43 (Gap43) was validated by western blotting.The behavioral results suggested that after 2 weeks of SCI, the rats were significantly induced to have a spastic reaction (P 0.05), while after 4 weeks of LIFU treatment, the spastic response of rats was significantly improved (P 0.05). Western blot analysis showed a significant increase in Gap43 expression in the SCI+LIFU(-) group compared with the sham group, whereas after 4 weeks of LIFU treatment, Gap43 protein expression was significantly decreased (P 0.05).The results of this study showed that LIFU is an alternative treatment that can effectively relieve spastic reactions caused by SCI, possibly by reducing abnormal neuroplasticity or axon regeneration below the SCI segment.

Ying Zhao,1,&ast; Liqing Yao,1,&ast; Lijuan Ao,2 Jibing Ou,1 Ying He,1 Yunyun Shang1 1The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China; 2School of Rehabilitation, Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijuan AoSchool of Rehabilitation, Kunming Medical University, Kunming, 650500, People’s Republic of ChinaTel +86 13508710081Fax +8687165338994Email lijuandrao@163.comObjective: In this study, umbilical cord mesenchymal stem cell (UC-MSC) transplantation was used to treat patients with spinal cord injury (SCI). The microstructural changes of the spinal cord before and after transplantation were observed by diffusion tensor imaging (DTI).Methods: From January 2014 to May 2015, seven patients who met the inclusion criteria were enrolled in this study. In the experimental group, both UC-MSC transplantation and comprehensive rehabilitation treatment were applied, while the control group received only comprehensive rehabilitation treatment. American Spinal Injury Association (ASIA) sensory and motor scores and the degree of SCI, spasticity, and urine/defecation functions were measured and evaluated together with DTI before the treatment and again at two and six months after the first treatment.Results: From the DTI, the changes in the fractional anisotropy (FA) value and the apparent diffusion coefficient (ADC) value were as follows: in the experimental group, there were significant differences in the FA and ADC values before and after treatment (P < 0.05) with a decreased ADC value and an increased FA value. The differences in the ADC and FA values of the normal layer and the lesion layer before and after treatment were compared. The differences in ADC and FA at the lesion layer before and after transplantation were greater than those of the normal layer, and the differences were statistically significant (P < 0.05). In the experimental group, one patient with incomplete SCI and one patient with a short course of complete SCI improved in terms of light touch, acupuncture sensation, and motor score. One patient with incomplete SCI achieved improvement in spasticity and urine/defecation functions.Conclusion: The combination of UC-MSC transplantation and comprehensive rehabilitation therapy could help to promote the structural repair of the spinal nerve in patients with SCI.Keywords: spinal cord injury, stem cell, DTI, ADC, FA

Alzheimer’s disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb—Gastrodia elata—and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

Focused ultrasound (FUS) combined with microbubbles (MBs) has recently emerged as a potential approach to open the blood-brain barrier (BBB) for delivering drugs into the brain. However, appropriate approaches are still lacking to monitor the sublethal damage during FUS-mediated BBB opening in vivo, especially the early stage cell apoptotic events. Here, we developed a kind of nanoprobe-loaded MBs (AV-ICG-NPs@MBs) which can monitor the apoptotic cells that occur during FUS-mediated BBB opening through encapsulating the annexin V-targeted nanoprobes AV-ICG-NPs into the cavity of lipid-PLGA hybrid MBs. When irradiated by FUS, AV-ICG-NPs@MBs in the cerebral blood vessels would produce cavitation, favoring the BBB opening. Meanwhile, AV-ICG-NPs@MBs would be destroyed and release their AV-ICG-NPs payload. These released AV-ICG-NPs can be further delivered into the brain via the destructed BBB and bind with the phosphatidylserine externalized on the membrane of apoptotic cells if this occurs, leading to the prolonged detention of fluorescent signals in the brain. Furthermore, we also provided an effective strategy to inhibit or reverse the possible damage to the brain from a FUS-mediated BBB opening technology, through developing AV-ICG-NPs/GAS@MBs that encapsulate the antioxidant gastrodin (GAS) into AV-ICG-NPs@MBs. Accompanied by FUS irradiation and bubble cavitation, GAS was released and delivered into the brain, where they scavenged the oxygen free radicals produced from cavitation, leading to significantly lower fluorescence signals in the brain due to the absence of externalized phosphatidylserine. In conclusion, our study provides an approach to monitor and inhibit cell apoptotic events during FUS-mediated BBB opening.

Focused ultrasound (FUS) is a potential tool for treating chronic pain by modulating the central nervous system. Herein, we aimed to determine whether transcranial FUS stimulation of the anterior cingulate cortex (ACC) effectively improved chronic pain in the chronic compress injury mice model at different stages of neuropathic pain. The mechanical threshold of pain was recorded in the nociceptive tests. We found FUS stimulation elevated the mechanical threshold of pain in both short-term ( p < 0.01 ) and long-term ( p < 0.05 ) experiments. Furthermore, we determined protein expression differences in ACC between the control group, the intervention group, and the Sham group to analyze the underlying mechanism of FUS stimulation in improving neuropathic pain. Additionally, the results showed FUS stimulation led to alterations in differential proteins in long-term experiments, including cellular processes, cellular signaling, and information storage and processing. Our findings indicate FUS may effectively alleviate mechanical neuropathic pain via the ACC’s stimulation, especially in the chronic state.

AIM To investigate the efficacy of a virtual reality rehabilitation system of wearable multi-inertial sensors to improve upper-limb function in children with brain injury. METHOD Eighty children (39 males, 41 females) with brain injury including cerebral palsy aged 3 to 16 years (mean age 5y 8mo, SD 2y 10mo) were assessed as part of a multicentre, single-blind, randomized controlled trial. The intervention group received a 30-minute virtual reality intervention and a 30-minute session of conventional occupational therapy while the control group received 60 minutes of conventional occupational therapy per session, with 20 sessions over 4 weeks. The virtual reality rehabilitation system consisted of games promoting wrist and forearm articular movements using wearable inertial sensors. The Melbourne Assessment of Unilateral Upper Limb Function-2 (MA-2), Upper Limb Physician's Rating Scale, Pediatric Evaluation of Disability Inventory Computer Adaptive Test, and computerized three-dimensional motion analysis were performed. RESULTS Both groups (virtual reality, n=40; control, n=38) significantly improved after treatment compared to baseline; however, the virtual reality group showed more significant improvements in upper-limb dexterity functions (MA-2, virtual reality group: Δ=10.09±10.50; control: Δ=3.65±6.92), performance of activities of daily living, and forearm supination by kinematic analysis (p

BACKGROUND: Previous studies in non-Chinese populations have found a relationship between performance on isometric trunk muscle endurance tests and low back pain (LBP). However, the relationship between trunk muscle endurance and LBP in Chinese populations has received little attention and age-referenced data have not been reported. OBJECTIVE: Evaluate the relationship between age-referenced isometric trunk muscle endurance values and LBP in a Chinese cohort. METHODS: One hundred and eighty-eight participants (20-59-years) performed four timed-endurance tests (Biering-Sorensen, plank, left/right side bridge) in random order. Participants with a history of LBP completed an Oswestry Disability Index (ODI) and pain scale. Holding-times for the four tests were summed and receiver operating characteristic (ROC) curve analysis was performed to differentiate participants with and without LBP. RESULTS: Data were grouped by age. Analysis revealed similar endurance values to those reported in non-Chinese populations, except longer holding times were recorded in the 50-59 yr Chinese cohort. Pain scores were positively correlated with ODI scores. ROC curve analysis showed that the area under the curve was 0.723 and optimal cut-off was 288 sec (sensitivity and specificity both 0.75). CONCLUSIONS: This study is the first to describe trunk muscle endurance reference data in Chinese people. Individuals with a summed endurance time of < 288 seconds appear more likely to suffer LBP.

The blood-cerebrospinal fluid barrier (BCSFB) is another gatekeeper between systemic circulation and the central nervous system (CNS), mainly present at the boundary between choroid plexuses and the ventricular system. This study demonstrates BCSFB opening in rats by single pulse of low-energy focused shockwave (FSW, energy flux density 0.03 mJ/mm2, 2 × 106 microbubbles/kg) treatment at lateral ventricle, resulting in significantly elevated cerebrospinal fluid (CSF) concentrations of systemically-administered gastrodin (GTD) (4 times vs. control within 3 hrs) that remained detectable for 24 hrs. The FSW-GTD group had significantly lower Racine’s scale (

Stem cell transplantation can promote functional restoration following acute spinal cord injury (injury time < 3 months), but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury (injury time > 6 months) were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury.

Background Ultrasonography is a convenient technique to investigate muscle properties and has been widely used to look into muscle functions since it is non-invasive and real-time. Muscle thickness, a quantification which can effectively reflect the muscle activities during muscle contraction, is an important measure for musculoskeletal studies using ultrasonography. The traditional manual operation to read muscle thickness is subjective and time-consuming, therefore a number of studies have focused on the automatic estimation of muscle fascicle orientation and muscle thickness, to which the speckle noises in ultrasound images could be the major obstacle. There have been two popular methods proposed to enhance the hyperechoic regions over the speckles in ultrasonography, namely Gabor Filtering and Multiscale Vessel Enhancement Filtering (MVEF). Methods A study on gastrocnemius muscle is conducted to quantitatively evaluate whether and how these two methods could help the automatic estimation of the muscle thickness based on Revoting Hough Transform (RVHT). The muscle thickness results obtained from each of the two methods are compared with the results from manual measurement, respectively. Data from an aged subject with cerebral infarction is also studied. Results It’s shown in the experiments that, Gabor Filtering and MVEF can both enable RVHT to generate comparable results of muscle thickness to those by manual drawing (mean ± SD, 1.45 ± 0.48 and 1.38 ± 0.56 mm respectively). However, the MVEF method requires much less computation than Gabor Filtering. Conclusions Both methods, as preprocessing procedure can enable RVHT the automatic estimation of muscle thickness and MVEF is believed to be a better choice for real-time applications.