Composition of the pericellular matrix modulates the deformation behaviour of chondrocytes in articular cartilage under static loading

The aim was to assess the role of the composition changes in the pericellular matrix (PCM) for the chondrocyte deformation. For that, a three-dimensional finite element model with depth-dependent collagen density, fluid fraction, fixed charge density and collagen architecture, including parallel planes representing the split-lines, was created to model the extracellular matrix (ECM). The PCM was constructed similarly as the ECM, but the collagen fibrils were oriented parallel to the chondrocyte surfaces. The chondrocytes were modelled as poroelastic with swelling properties. Deformation behaviour of the cells was studied under 15% static compression. Due to the depth-dependent structure and composition of cartilage, axial cell strains were highly depth-dependent. An increase in the collagen content and fluid fraction in the PCMs increased the lateral cell strains, while an increase in the fixed charge density induced an inverse behaviour. Axial cell strains were only slightly affected by the changes in PCM composition. We conclude that the PCM composition plays a significant role in the deformation behaviour of chondrocytes, possibly modulating cartilage development, adaptation and degeneration. The development of cartilage repair materials could benefit from this information

T4TE: Team for TMS−EEG to improve reproducibility through an open collaborative initiative

Funding Information: M.B. and A.Z. were supported by the Italian Ministry of Health - "Ricerca Corrente". PJ and TPM acknowledge funding from the Academy of Finland (grant number: 322423 and 321631 ).Peer reviewe

Stress-relaxation of human patellar articular cartilage in unconfined compression: Prediction of mechanical response by tissue composition and structure.

Mechanical properties of articular cartilage are controlled by tissue composition and structure. Cartilage function is sensitively altered during tissue degeneration, in osteoarthritis (OA). However, mechanical properties of the tissue cannot be determined non-invasively. In the present study, we evaluate the feasibility to predict, without mechanical testing, the stress–relaxation response of human articular cartilage under unconfined compression. This is carried out by combining microscopic and biochemical analyses with composition-based mathematical modeling.Cartilage samples from five cadaver patellae were mechanically tested under unconfined compression. Depth-dependent collagen content and fibril orientation, as well as proteoglycan and water content were derived by combining Fourier transform infrared imaging, biochemical analyses and polarized light microscopy. Finite element models were constructed for each sample in unconfined compression geometry. First, composition-based fibril-reinforced poroviscoelastic swelling models, including composition and structure obtained from microscopical and biochemical analyses were fitted to experimental stress–relaxation responses of three samples. Subsequently, optimized values of model constants, as well as compositional and structural parameters were implemented in the models of two additional samples to validate the optimization.Theoretical stress–relaxation curves agreed with the experimental tests (R=0.95–0.99). Using the optimized values of mechanical parameters, as well as composition and structure of additional samples, we were able to predict their mechanical behavior in unconfined compression, without mechanical testing (R=0.98). Our results suggest that specific information on tissue composition and structure might enable assessment of cartilage mechanics without mechanical testing

Corticospinal excitability in idiopathic normal pressure hydrocephalus:a transcranial magnetic stimulation study

Abstract Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability. Methods: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67–84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input–output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture. Results: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049). Conclusions: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment

TMS combined with EEG: recommendations and open issues for data collection and analysis

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS−EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS−EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS−EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS−EEG covered all aspects that should be considered in TMS−EEG experiments, providing methodological recommendations (when possible) for effective TMS−EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS−EEG methodology and thus may promote standardization of experimental and computational procedures across groups