Histological confirmation and biological significance of cartilage canals demonstrated using high field MRI in swine at predilection sites of osteochondrosis

Cartilage canal vessels in epiphyseal cartilage have a pivotal role in the pathogenesis of osteochondrosis/osteochondritis dissecans. The present study aimed to validate high field magnetic resonance imaging (MRI) methods to visualize these vessels in young pigs. Osteochondral samples from the distal femur and distal humerus (predilection sites of osteochondrosis) of piglets were imaged post‐mortem: (1) using susceptibility‐weighted imaging (SWI) in an MRI scanner, followed by histological evaluation; and (2) after barium perfusion using µCT, followed by clearing techniques. In addition, both stifle joints of a 25‐day‐old piglet were imaged in vivo using SWI and gadolinium enhanced T1‐weighted MRI, after which distal femoral samples were harvested and evaluated using µCT and histology. Histological sections were compared to corresponding MRI slices, and three‐dimensional visualizations of vessels identified using MRI were compared to those obtained using µCT and to the cleared specimens. Vessels contained in cartilage canals were identified using MRI, both ex vivo and in vivo; their locations matched those observed in the histological sections, µCT images, and cleared specimens of barium‐perfused tissues. The ability to visualize cartilage canal blood vessels by MRI, without using a contrast agent, will allow future longitudinal studies to evaluate their role in developmental orthopedic disease. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:2006–2012, 2013     

Masked repetition priming effects on naming in aphasia: A Phase I treatment study

Background: It has been suggested that lexical access deficits in aphasia may be the result of impaired automatic activation of the networks that support language processing, a system that operates implicitly, outside conscious awareness. This raises the question of whether there might be a way to address rebuilding these implicit networks directly, rather than through the explicit treatment protocols that are typical of aphasia therapy. Masked priming is one method by which the language system can be automatically activated, while limiting or preventing the influence of conscious, explicit processing.

Aims: This Phase I study was undertaken to investigate the potential effectiveness of masked repetition priming as a treatment for anomia.

Methods & Procedures: This study used a single-participant, ABA, multiple-baseline repeated-probe design. A total of 22 training sessions were completed across 4 weeks. Training involved repeated presentation of masked repetition primes paired with target pictures prior to attempts at naming those pictures. Untrained items were presented an equal number of times, but without prime words. Repeated naming probes administered before, during, and after treatment were used to measure effects of training (naming trained stimuli) and generalisation (naming within and across semantic categories). Pre- and post-training assessment with broader tests of language function and conversation were also completed.

Outcomes & Results: Results revealed a small effect of training on naming of trained items in one category, as well as a pattern of improvement in the other category that did not quite meet the criterion for a small effect. There was also a medium cross- category generalisation effect, although no generalisation effect was seen to untrained items within semantic categories. Improvements were seen on some measures of general language function.

Conclusions: Masked priming can elicit changes in naming ability over time, and may have potential as a tool for improving word retrieval in individuals with anomia. Results warrant further investigation.     

Glia cell line‐derived neurotrophic factor mediates survival of murine sympathetic precursors

During embryonic development, neurons are first produced in excess, and final numbers are adjusted by apoptosis at later stages. Crucial to this end is the amount of target‐derived growth factor available for the neurons. By this means, the target size correctly matches the innervating neuron number. This target‐derived survival has been well studied for sympathetic neurons, and nerve growth factor (NGF) was identified to be the crucial factor for maintaining sympathetic neurons at late embryonic and early postnatal stages, with a virtual complete loss of sympathetic neurons in NGF knockout (KO) mice. This indicates that all sympathetic neurons are dependent on NGF. However, also different glia cell line‐derived neurotrophic factor (GDNF) KO mice consistently presented a loss of sympathetic neurons. This was the rationale for investigating the role of GDNF for sympathetic precursor/neuron survival. Here we show that GDNF is capable of promoting survival of 30% sympathetic precursors dissociated at E13. This is in line with data from GDNF KOs in which a comparable sympathetic neuron loss was observed at late embryonic stages, although the onset of the phenotype was unclear. We further present data showing that GDNF ligand and canonical receptors are expressed in sympathetic neurons especially at embryonic stages, raising the possibility of an autocrine/paracrine GDNF action. Finally, we show that GDNF also maintained neonatal sympathetic neurons (40%) cultured for 2 days. However, the GDNF responsiveness was lost at 5 days in vitro. © 2013 Wiley Periodicals, Inc.     

Automatic Control of Veno‐Venous Extracorporeal Lung Assist

Veno‐venous extracorporeal lung assist (ECLA) can provide sufficient gas exchange even in most severe cases of acute respiratory distress syndrome. Commercially available systems are manually controlled, although an automatically controlled ECLA could allow individualized and continuous adaption to clinical requirements. Therefore, we developed a demonstrator with an integrated control algorithm to keep continuously measured peripheral oxygen saturation and partial pressure of carbon dioxide constant by automatically adjusting extracorporeal blood and gas flow. The “SmartECLA” system was tested in six animal experiments with increasing pulmonary hypoventilation and hypoxic inspiratory gas mixture to simulate progressive acute respiratory failure. During a cumulative evaluation time of 32 h for all experiments, automatic ECLA control resulted in a peripheral oxygen saturation ≥90% for 98% of the time with the lowest value of 82% for 15 s. Partial pressure of venous carbon dioxide was between 40 and 49 mm Hg for 97% of the time with no value <35 mm Hg or >49 mm Hg. With decreasing inspiratory oxygen concentration, extracorporeal oxygen uptake increased from 68 ± 25 to 154 ± 34 mL/min (P < 0.05), and reducing respiratory rate resulted in increasing extracorporeal carbon dioxide elimination from 71 ± 37 to 92 ± 37 mL/min (P < 0.05). The “SmartECLA” demonstrator allowed reliable automatic control of the extracorporeal circuit. Proof of concept could be demonstrated for this novel automatically controlled veno‐venous ECLA circuit.     

Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression

Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3(-/-) mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3(-/-) mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia.     

Contribution of individual retinal ganglion cell responses to velocity and acceleration encoding

We investigate the capability of turtle retinal ganglion cell (RGC) ensembles to simultaneously encode multiple aspects of visual motion: speed, direction, and acceleration of moving patterns. Bayesian stimulus reconstruction reveals that the instantaneous firing rates of RGCs contain information about all of these stimulus properties. Stimulus velocity is mainly encoded by steady-state firing rates, whereas acceleration can be reconstructed from transient components in RGC activity induced by abrupt velocity changes. Therefore neurons in higher brain areas may in principle extract information about changing velocity from the instantaneous firing activity of RGCs, without the need to compare responses to present velocities to previous ones. However, reconstruction requires the estimation of a combined acceleration and velocity signal, indicating that RGC ensembles signal both properties simultaneously. In accordance with this conclusion, combined velocity/acceleration sensitivity enhances the similarity of artificial spike trains to experimental data by 50% compared with the case of pure velocity tuning. Decoding of motion direction in addition to speed and acceleration requires direction-sensitive cells, which generate higher firing rates for one of the motion directions and therefore show asymmetric velocity tuning. By dividing the entire ensemble of simultaneously recorded cells into one group of direction-sensitive cells and one group with symmetric tuning, we demonstrate that the population of direction-sensitive cells encodes a combination of motion speed, acceleration, and direction. However, estimation of velocity and acceleration is improved by including the larger group of RGC responses that are sensitive to speed but not to motion direction.