Changes In Fiber Density Research Articles

Aerobic exercise is associated with region-specific changes in volumetric, tensor-based, and fixel-based measures of white matter integrity in healthy older adults

White matter integrity and cognition have been found to decline with advancing adult age. Aerobic exercise may be effective in counteracting these declines. Generally, white matter integrity has been quantified using a volumetric measure (WMV) and with tensor-based parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), the validity of which appears to be compromised in the presence of crossing fibers. Fixel-based analysis techniques claim to overcome this problem by yielding estimates of fiber density (FD), cross-section (FC), and their product (FDC) in multiple directions per voxel. In a sample of 61 healthy older adults (63–76 years old), we quantified changes in white matter integrity following an aerobic exercise intervention with the commonly used volumetric and tensor-based metrics (WMV, FA, MD) and with fixel-based metrics (FD, FC, FDC). We investigated the associations of changes in these white matter parameters with changes in cardiovascular fitness and Digit Symbol Substitution task (DSST) performance, a marker of perceptual speed. In line with previous findings, we observed maintained WMV in the corpus callosum of exercisers, and positive change-change correlations between WMV and fitness, and between WMV and perceptual speed. For FA and MD, group differences in change opposite to those hypothesized were found in the corpus callosum, posterior corona radiata, and superior longitudinal fasciculus at an uncorrected significance threshold. Likewise, regions in superficial WM in the prefrontal cortex showed group differences in FD and FDC change, uncorrected, with more positive change in controls and more negative change in exercisers. Finally, changes in FD and FDC were found to be inversely correlated to changes in fitness and DSST performance. The present results corroborate previous findings of WMV changes, but cast doubt on current physiological interpretations of both tensor-based and fixel-based indicators of white matter properties in the context of exercise intervention studies.

Six Months of Piano Training in Healthy Elderly Stabilizes White Matter Microstructure in the Fornix, Compared to an Active Control Group.

While aging is characterized by neurodegeneration, musical training is associated with experience-driven brain plasticity and protection against age-related cognitive decline. However, evidence for the positive effects of musical training mostly comes from cross-sectional studies while randomized controlled trials with larger sample sizes are rare. The current study compares the influence of six months of piano training with music listening/musical culture lessons in 121 musically naïve healthy elderly individuals with regard to white matter properties using fixel-based analysis. Analyses revealed a significant fiber density decline in the music listening/musical culture group (but not in the piano group), after six months, in the fornix, which is a white matter tract that naturally declines with age. In addition, these changes in fiber density positively correlated to episodic memory task performances and the amount of weekly piano training. These findings not only provide further evidence for the involvement of the fornix in episodic memory encoding but also more importantly show that learning to play the piano at an advanced age may stabilize white matter microstructure of the fornix.

White matter fiber density for vocabulary better maintained than fluid abilities in aging

AbstractBackgroundAging research has repeatedly shown that crystallized abilities, cognitive processes reliant on learned knowledge, are well preserved well into old age. On the other hand, fluid abilities, processes that are not knowledge‐dependent, show decline as early as the third decade of life. It is still unclear what mechanism enables the two starkly contrasting aging trajectories to exist all within the same brains.MethodFrom the Reference Ability Neural Network (RANN) study, 181 participants (age=51.2±17.2, 101females) with both baseline and 5‐year follow‐up diffusion weighted imaging data were included in the current analysis. Based on fMRI activation data, the set of brain regions were derived that are associated with performance of each of four cognitive abilities: vocabulary, processing speed, episodic memory, and reasoning. Using these regions as seeds, white matter tracts connecting the brain regions for each ability were extracted and used to calculate the mean fiber density associated with each ability. Three models, linear, partial linear, and quadratic were performed to model the longitudinal changes in fiber density for each ability. Mixed effect regression was used to test whether vocabulary, the only crystallized ability, shows more gradual decline than white matter for the other three abilities, which were all fluid abilities. The non‐linear trend of age was modeled using B‐splines with the knot point selection based on Bayesian information criteria (BIC).ResultConsistent with cross‐sectional results reported in Gazes et al. 2020, mean fiber density for white matter tracts associated with the vocabulary ability was shown to follow a slower decline with age than that for the three fluid abilities – processing speed [F(2,1251)=57.5, p<.001], episodic memory [F(2,1251)=5.32, p<.001), and reasoning [F(2,1251)=4.05, p<.001]. Figure 1 shows the age‐related trajectory modeled with quadratic trend, which was the best fitting model based on BIC values. Vocabulary, in purple, clearly demonstrates a shallower decline than the other three abilities for fiber density.ConclusionThis study demonstrated that longitudinal changes in the microstructural integrity of white matter tracts are better preserved for vocabulary, a crystallized ability, than that for the three fluid abilities, suggesting that preservation of white matter contributes to the maintenance of crystallized abilities with age.

Cognitive Training in Parkinson\u2019s Disease Induces Local, Not Global, Changes in White Matter Microstructure

Previous studies showed that cognitive training can improve cognitive performance in various neurodegenerative diseases but little is known about the effects of cognitive training on the brain. Here, we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and structural network topology. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N = 40 cognitive training group, N = 39 active control group) underwent multi-shell diffusion-weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed investigating white matter microstructural integrity (e.g., fractional anisotropy) in five tracts of interest, including the anterior thalamic radiation (ATR), whole-brain tract-based spatial statistics (TBSS), and the topology of the structural network. Relative to the active control condition, cognitive training had no effect on topology of the structural network or whole-brain TBSS. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B [SE]: − 0.32 [0.12], P = 0.01). This reduction was associated with faster responses on the Tower of London task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P < 0.006). Post hoc “fixel-based” analyses showed that this was not due to changes in fiber density and cross section. This suggests that the observed effect in the ATR is due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that 8 weeks of cognitive training does not alter network topology, but has subtle local effects on structural connectivity.

Characterization of Calcium Hydroxide-treated Zalacca Fibers for Improving Properties as Reinforcement for Composites

Chemical treatment is done to enhance characteristics of plant fibers and its interfacial compatibility with polymer matrix. Calcium hydroxide is an environmental-friendly alternative. This research aims to explore the influence of calcium hydroxide treatment on chemical, physical, thermal, morphological, and mechanical characteristics of zalacca fibers as reinforcements for composites. The time of treatment were varied for 24, 48, and 72 h. Fiber content analysis, XRD, FTIR, TGA-DTA, SEM, density, and single fiber tensile testing were performed. The percentage of cellulose was decreased meanwhile hemicellulose and lignin were increased. There was a decrease in crystallinity and crystallinity index after Ca(OH)2 treatment. The treatment induced some chemical groups correlated to the slight increase of lignin and hemicellulose percentage. There was an improvement of thermal stability of the fiber up to 200°C. The observation using SEM revealed that there were cleaning and roughing effect on fiber surface. There was no significant change in fiber density due to the treatment. However, the tensile strength and elastic modulus were improved after Ca(OH)2 treatment but the decline happened in a longer time of treatment. Accordingly, Ca(OH)2 treatment up to 24 h is appropriate in enhancing the properties of zalacca fibers as composite reinforcements.

Visual Dysfunction Predicts Cognitive Impairment and White Matter Degeneration in Parkinson's Disease.

ABSTRACTBackgroundVisual dysfunction predicts dementia in Parkinson's disease (PD), but whether this translates to structural change is not known. The objectives of this study were to identify longitudinal white matter changes in patients with Parkinson's disease and low visual function and also in those who developed mild cognitive impairment.MethodsWe used fixel‐based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low visual function/55 intact vision and 13 PD‐mild cognitive impairment/51 normal cognition) and 25 controls and again after 18 months. We compared microstructural changes in fiber density, macrostructural changes in fiber bundle cross‐section and combined fiber density and cross‐section, across white matter, adjusting for age, sex, and intracranial volume.ResultsPatients with PD and visual dysfunction showed worse cognitive performance at follow‐up and were more likely to develop mild cognitive impairment compared with those with normal vision (P = 0.008). Parkinson's with poor visual function showed diffuse microstructural and macrostructural changes at baseline, whereas those with mild cognitive impairment showed fewer baseline changes. At follow‐up, Parkinson's with low visual function showed widespread macrostructural changes, involving the fronto‐occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in those with mild cognitive impairment at baseline or converters, even when the 2 groups were combined.ConclusionParkinson's patients with poor visual function show increased white matter damage over time, providing further evidence for visual function as a marker of imminent cognitive decline. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Microstructural Alterations in Hippocampal Subfields Mediate Age-Related Memory Decline in Humans.

Aging, even in the absence of clear pathology of dementia, is associated with cognitive decline. Neuroimaging, especially diffusion-weighted imaging, has been highly valuable in understanding some of these changes in live humans, non-invasively. Traditional tensor techniques have revealed that the integrity of the fornix and other white matter tracts significantly deteriorates with age, and that this deterioration is highly correlated with worsening cognitive performance. However, traditional tensor techniques are still not specific enough to indict explicit microstructural features that may be responsible for age-related cognitive decline and cannot be used to effectively study gray matter properties. Here, we sought to determine whether recent advances in diffusion-weighted imaging, including Neurite Orientation Dispersion and Density Imaging (NODDI) and Constrained Spherical Deconvolution, would provide more sensitive measures of age-related changes in the microstructure of the medial temporal lobe. We evaluated these measures in a group of young (ages 20–38 years old) and older (ages 59–84 years old) adults and assessed their relationships with performance on tests of cognition. We found that the fiber density (FD) of the fornix and the neurite density index (NDI) of the fornix, hippocampal subfields (DG/CA3, CA1, and subiculum), and parahippocampal cortex, varied as a function of age in a cross-sectional cohort. Moreover, in the fornix, DG/CA3, and CA1, these changes correlated with memory performance on the Rey Auditory Verbal Learning Test (RAVLT), even after regressing out the effect of age, suggesting that they were capturing neurobiological properties directly related to performance in this task. These measures provide more details regarding age-related neurobiological properties. For example, a change in fiber density could mean a reduction in axonal packing density or myelination, and the increase in NDI observed might be explained by changes in dendritic complexity or even sprouting. These results provide a far more comprehensive view than previously determined on the possible system-wide processes that may be occurring because of healthy aging and demonstrate that advanced diffusion-weighted imaging is evolving into a powerful tool to study more than just white matter properties.

Clinical duration of action of different botulinum toxin types in humans

The Botulinum NeuroToxin (BoNT) comprises several serotypes with distinct properties, mechanisms of action, sensitivity and duration of effect in different species. The serotype A (BoNT/A) is the prevalent neurotoxin applied in human's disease. In this paper we present an overview of the current knowledge regarding the duration of effect and the neuromuscular sprouting of different BoNT serotypes in humans. Then, we report the original results of a study in healthy subjects treated with BoNT/A, B, C and F using different neurophysiological techniques. Twelve healthy volunteers (7 men, 5 women) are treated with BoNT/A, B, C and F or placebo in Abductor digiti minimi (ADM) muscle of the hand. Before and after injections, an extensive neurophysiological study is performed with the CMAP amplitude variation, Multi-Motor Unit Action Potentials (MUAPs) analysis, the Turns/Amplitude ratio of interference pattern (IP) and determination of jitter and Fiber Density (FD) at single-fiber electromyography (SFEMG), at week 2 (w2), 4 (w4), 6 (w6) and 8 (w8). A maximal neuromuscular block is obtained at w2 for all the serotypes. Afterwards, the CMAP trend appear similar for BoNT/A, B, and C while, BoNT/F shows a faster recover. Multi-MUAPs analysis and IP detect mild changes at w2 for all serotypes, except for BoNT/F that shows a greater change since w4. SFEMG have minimal changes in FD while, Jitter increase at w2 with a slower decrease over the time for all BoNTs. In conclusion, BoNT/F has earlier sprouting and complete recovery at w8. Other serotypes present a slower and similar profile. The EMG appear useful to study the functional recovery in humans, and these results should provide new evidence for assessing different serotypes. These findings improve our knowledge regarding the methods to evaluate duration of effects and dose equivalents in different serotypes, that in the future could change the clinicians strategy for disease-tailored BoNT therapies.

Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction.

ObjectiveTo investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia.MethodsWe performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system.ResultsPatients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus.ConclusionsWe demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations.

Early childhood development of white matter fiber density and morphology

Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track developmental changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed “fixels”. Fixel-based analysis and mixed-effects models were used to assess tract-wise changes in fiber density and bundle morphology in 73 girls scanned at baseline (ages 4.09–7.02, mean ​= ​5.47, SD ​= ​0.81), 6-month (N ​= ​7), and one-year follow-up (N ​= ​42). For comparison, we also assessed changes in commonly utilized diffusion tensor metrics: fractional anisotropy (FA), and mean, radial and axial diffusivity (MD, RD, AD). Maturational increases in fixel-metrics were seen in most major white matter tracts, with the most rapid increases in the corticospinal tract and slowest or non-significant increases in the genu of the corpus callosum and uncinate fasciculi. As expected, we observed developmental increases in FA and decreases in MD, RD and AD, though percent changes were smaller relative to fixel-metrics. The majority of tracts showed more substantial morphological than microstructural changes. These findings highlight early childhood as a period of dynamic white matter maturation, characterized by large increases in macroscopic fiber bundle size, mild changes in axonal density, and parallel, albeit less substantial, changes in diffusion tensor metrics.

Noninvasive Induction of Muscle Fiber Hypertrophy and Hyperplasia: Effects of High-Intensity Focused Electromagnetic Field Evaluated in an In-Vivo Porcine Model: A Pilot Study.

BackgroundHigh-intensity focused electromagnetic (HIFEM) field technology has been reported to increase muscle thickness and hypertrophy. However, this process has not yet been confirmed on a histologic level.ObjectivesThe aim of this study was to evaluate in-vivo structural changes in striated porcine muscle tissue following HIFEM treatment.MethodsThree Yorkshire pigs received four 30-minute HIFEM treatments applied to the biceps femoris muscle on 1 side only. The fourth pig served as a control subject. At baseline and 2 weeks after the last treatment, biopsy specimens of the muscle tissue were collected from the treatment site. The control pig underwent muscle biopsy from a similar but untreated site. Twenty-five histology slides were evaluated from each pig. A certified histopathologist analyzed sliced biopsy samples for structural changes in the tissue.ResultsHistologic analysis showed hypertrophic changes 2 weeks posttreatment. The muscle mass density increased by 20.56% (to a mean of 17,053.4 [5617.9] µm2) compared with baseline. Similarly, muscle fiber density (hyperplasia) increased: the average change in the number of fibers in a slice area of 136,533.3 µm2 was +8.0%. The mean size of an individual muscle fiber increased by 12.15% (to 332.23 [280.2] µm2) 2 weeks posttreatment. Control samples did not show any significant change in fiber density or hyperplasia.ConclusionsHistopathologic quantification showed significant structural muscle changes through a combination of fiber hypertrophy and hyperplasia. Control biopsies showed a lack of similar changes. The data correlate with findings of other HIFEM research and suggest that HIFEM could be used for noninvasive induction of muscle growth.

Subtle white matter alterations in schizophrenia identified with a new measure of fiber density

Altered cerebral connectivity is one of the core pathophysiological mechanism underlying the development and progression of information-processing deficits in schizophrenia. To date, most diffusion tensor imaging (DTI) studies used fractional anisotropy (FA) to investigate disrupted white matter connections. However, a quantitative interpretation of FA changes is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of white matter alterations could be achieved by measuring fiber density (FD) - a novel non-tensor-derived diffusion marker. This study investigates, for the first time, FD alterations in schizophrenia patients. FD and FA maps were derived from diffusion data of 25 healthy controls (HC) and 21 patients with schizophrenia (SZ). Using tract-based spatial statistics (TBSS), group differences in FD and FA were investigated across the entire white matter. Furthermore, we performed a region of interest (ROI) analysis of frontal fasciculi to detect potential correlations between FD and positive symptoms. As a result, whole brain TBSS analysis revealed reduced FD in SZ patients compared to HC in several white matter tracts including the left and right thalamic radiation (TR), superior longitudinal fasciculus (SLF), corpus callosum (CC), and corticospinal tract (CST). In contrast, there were no significant FA differences between groups. Further, FD values in the TR were negatively correlated with the severity of positive symptoms and medication dose in SZ patients. In summary, a novel diffusion-weighted data analysis approach enabled us to identify widespread FD changes in SZ patients with most prominent white matter alterations in the frontal and subcortical regions. Our findings suggest that the new FD measure may be more sensitive to subtle changes in the white matter microstructure compared to FA, particularly in the given population. Therefore, investigating FD may be a promising approach to detect subtle changes in the white matter microstructure of altered connectivity in schizophrenia.

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event.SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of their influence on the whole-brain networks. Here, we have longitudinally and noninvasively monitored the structural and functional network alterations in the mouse model of focal cerebral ischemia. Structural changes of fiber-density increases are stimulated in the endogenous tissue without further modulation by the stem cells, while functional networks are stabilized by the stem cells via a paracrine effect. These results will help decipher the underlying networks of brain plasticity in response to cerebral lesions and offer clues to unravelling the mystery of how stem cells mediate regeneration.

The effect of different intensity exercise on skeletal muscle fiber MHC subtype transformation and CaN/NFATc1 signaling pathways

To study the effect of different intensity exercise on skeletal muscle fiber myosin heavy chain(MHC) subtype transformation and CaN/NFATc1 signaling pathways. Twenty-four Male SD rats (2-month old) were randomly divided into normal control group (NC), moderate intensity exercise group (ME, grade 5°, speed 18 m/min), heavy intensity exercise group (HE, grade 10°, 26.8 m/min). The rats in exercise groups were treated with treadmill training for eight weeks. The type I and type Ⅱ muscle fibers were determined by ATPase staining method. MHC subtype was separated by SDS-PAGE. The activity of CaN was determined by colorimetric method. The content of NFATc1 protein in skeletal muscle was detected by immune imprinting technology. ①Skeletal muscle fiber density changes:the type I and Ⅱ fiber number density of quadriceps in ME group were increased significantly (P<0.05), but in HE group, only the type Ⅱ fiber surface density was increased significantly (P<0.05). The type I fiber number density of soleus in ME and HE group was increased significantly (P<0.05). ②The changes of fibers MHC subtype percentage in skeletal muscle:the percentages of MHC I and type Ⅱa of quadriceps in ME group were increased (P<0.05), while the percentage of MHC Ⅱb was decrease (P<0.05). The percentage of MHC I in soleus was increased, while the percentages of MHCⅡa and Ⅱb were decreased. ③The activity of CaN and the content of NFATc1 protein in ME group were increased significantly (P<0.05). The heavy and moderate intensity exercise may induce skeletal muscle MHC type transforming from fast to slow. At the same time, the activity of CaN and the expression of NFATc1 protein are increased accompanying the changes of skeletal muscle fibers subtype.

Encasement of metallic cardiovascular stents with endothelial cell‐selective copolyetheresterurethane microfibers

Cardiovascular metallic stents established in clinical application are typically coated by a thin polymeric layer on the stent struts to improve hemocompatibility, whereby often a drug is added to the coating to inhibit neointimal hyperplasia. Besides such thin film coatings recently nano/microfiber coated stents are investigated, whereby the fibrous coating was applied circumferential on stents. Here, we explored whether a thin fibrous encasement of metallic stents with preferentially longitudinal aligned fibers and different local fiber densities can be achieved by electrospinning. An elastic degradable copolyetheresterurethane, which is reported to selectively enhance the adhesion of endothelial cells, while simultaneously rejecting smooth muscle cells, was utilized for stent coating. The fibrous stent encasements were microscopically assessed regarding their single fiber diameters, fiber covered area and fiber alignment at three characteristic stent regions before and after stent expansion. Stent coatings with thicknesses in the range from 30 to 50 µm were achieved via electrospinning with 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFP)‐based polymer solution, while a mixture of HFP and formic acid as solvent resulted in encasements with a thickness below 5 µm comprising submicron sized single fibers. All polymeric encasements were mechanically stable during expansion, whereby the fibers deposited on the struts remained their position. The observed changes in fiber density and diameter indicated diverse local deformation mechanisms of the microfibers at the different regions between the struts. Based on these results it can be anticipated that the presented fibrous encasement of stents might be a promising alternative to stents with polymeric strut coatings releasing anti‐proliferative drugs. Copyright © 2015 John Wiley &amp; Sons, Ltd.

Mechanics and Structure of Fibrin Networks Polymerized under Oscillatory Shear Perturbations

The mechanical properties of a blood clot are of crucial importance for its ability to stem the flow of blood at a site of vascular injury. These properties are largely determined by the underlying structural scaffold which forms during blood coagulation, a branched network of the biopolymer fibrin. Alterations in the structure of this network, such as changes in fiber density, fiber thickness or branching probability, strongly affect the mechanics of the network.The relationship between network architecture and bulk-level mechanics is commonly investigated using in vitro fibrin networks polymerized under static conditions. However, in the body, blood clots form under a highly dynamic mechanical environment: Nascent fibrin fibers are constantly exposed to the pulsatile shear flow of blood and the concurrent oscillatory dilation of the vessel walls. However, the effects of mechanical perturbations during polymerization on clot structure and the resultant mechanical properties remain unknown.Here, we polymerize fibrin networks while applying continuous oscillatory shear perturbations of varying strain amplitude. Despite these mechanical perturbations, fibrin can form rigid clots which exhibit a significantly later onset of the non-linear strain-stiffening response, a postponed rupture strain, and a lowered linear modulus compared to clots formed without perturbations. Up to perturbation amplitudes of 45% shear strain, the typical non-linear stiffness of these clots as well as their rupture stresses are of similar magnitude to those formed without perturbation. We show by confocal microscopy that these changes in the mechanical properties result from a formation of two architecturally distinct layers within the clot: one layer shows a highly bundled structure, while the other layer is virtually unaltered. This architectural adjustment may serve as a means for adapting blood clots to the mechanical loading conditions of the environment in which they form.

EMG changes in myofascial trigger point after type A botulinum toxin

Neuro-muscular dysfunction with abnormal activity of motor endplates (EP) plays a major role in the origin of a myofascial trigger point (MTP). Intramuscular injection of type A botulinum toxin (BT-A) leads to two effects: direct inhibition of extrafusal muscular fibers and inhibition of muscle spindle activity. Clinical effect is noticeable muscle relaxation and muscle pain relief. We investigated 12 patients with myofascial pain. The control group consisted of 12 healthy volunteers with the same sex and age distribution. From 50 to 100 MU (depending on the size and stage of MTP) of BT-A (Dysport) was injected under EMG control in the MTP of the horizontal part of trapezius muscle. Conventional and single-fiber EMG were done for all patients before BT-A injection, 1 week, 4 months and 1 year after. EP noise in MTP zone was recorded much more frequently than separate spikes. EMG before BT-A injection revealed typical signs of MTP. After 7 days EMG revealed fibrillation potentials, decrease of amplitude and duration of motor unit potentials (MUP) in the injected muscle. There was no change in fiber density. One month after BT-A injection was characterized by normal MUP duration, which is the most sensitive to functional reorganization of motor unit. After 4 months we noticed the tendency for normalization of all MUP parameters. Maximal decrease of fiber density was observed 1 and 4 months after BT-A injection. At 1 year after BT-A injection there was normalization of fiber density.

Distribution and origin of vesicular glutamate transporter 2-immunoreactive fibers in the rat hippocampus.

This study examined the distribution of vesicular glutamate transporter 2 (VGLUT2)-immunoreactive neuronal structures in the ipsilateral and contralateral hippocampi of unilateral fimbria/fornix transected, unilateral entorhinal cortex ablated, and intact female and male rats. In the hippocampi of intact animals, the highest density of VGLUT2-positive boutons was observed in the supragranular layer of the dentate gyrus, followed by the CA2 pyramidal and oriens layers, and the stratum lacunosum-moleculare of the CA1 field. This staining pattern was identical both in males and in females. Electron microscopic examination revealed that the immunolabeling was confined to axon terminals forming exclusively asymmetric synaptic contacts. The quantitative analysis of the synaptic targets of VGLUT2-positive terminals showed that in the dentate gyrus, 59% of the synaptic targets were dendritic spines, followed by dendritic shafts (22%) and granule cell somata (19%). In the pyramidal layer of the CA2 field, VGLUT2-immunoreactive boutons contacted mostly dendritic shafts (85%), only some of which (15%) synapsed with spines. The synaptic targets of VGLUT2-positive varicosities were dendritic spines (71%) and shafts (29%) in the stratum lacunosum-moleculare of the CA1 field. The fimbria/fornix transection caused a significant reduction in the density of VGLUT2-positive boutons only in the CA2 field, while entorhinal cortex ablation elicited no change in fiber density in any of the areas analyzed. Furthermore, our latest experiments on colchicine-treated animals revealed a large population of VGLUT2-positive neurons in the hippocampus that may be a possible intrinsic source of hippocampal VGLUT2 boutons. Our results suggest that the most likely sources of VGLUT2-positive boutons in the dentate supragranular layer, the CA2 area, as well as in the stratum lacunosum-moleculare of the CA1 field, might be the mossy cells, the supramammillary area, and the nucleus reuniens thalami, respectively.

Effects of denervation on posterior cricoarytenoid muscle physiology and histochemistry.

The effects of chronic posterior cricoarytenoid muscle denervation were assessed at 3 and 7 months in 26 animals following resection of 10 cm of recurrent laryngeal nerve with stump ligation. The physiology of denervation was characterized by a decrease in contraction strength and an increase in contraction time. The reduction in contraction strength reflected the loss in muscle weight and atrophic changes in fiber density and diameter. A change in muscle composition occurred because of the increased susceptibility of fast-twitch (type 2) fibers to degeneration. However, the compositional change alone could not account for the slowing of muscle contraction. Muscle fibrosis was negligible at 3 months, but encompassed one third of the fiber population by 7 months. In view of the irreversible nature of fibrosis, this study suggested that clinical intervention to rescue denervated posterior cricoarytenoid muscle fibers should be delayed no longer than 7 months to improve the chances for full recovery.

Skeletal muscle atrophy in response to 14 days of weightlessness: vastus medialis

The vastus medialis (VM) from rats after 14 days of microgravity on COSMOS 2044 (F) was compared with VM from tail-suspended hindlimb-unloaded rats (T) and ground controls, including vivarium (V), synchronous (S), and basal (B) animals. The VM is composed chiefly of fast-twitch fibers; however, it contains a deep portion closer to the bone with mixed slow- and fast-twitch fibers. In the mixed-fiber portion, type I and II fiber areas were significantly reduced in F animals. In the homogeneous portion with chiefly fast-twitch fibers, F rats also showed reductions in cross-sectional areas compared with T, V, and B but not S rats. Fiber densities (fibers/mm2) were greatest in VM from F rats. Capillary density changes paralleled fiber density changes. F animals have significantly greater density of capillaries in the mixed-fiber portion. Concentrations of protein, RNA, and DNA were highest in V controls, whereas F rats had the lowest level of total RNA. Lactate dehydrogenase activity, one measure of anaerobic capacity, was greater in F than in S rats. Citrate synthase activity, a measure of oxidative capacity, showed no significant differences between groups. Although triglyceride stores of VM were greater in F than in T rats, there were no significant differences from any of the control groups. It was concluded that VM wet weights may be a less sensitive measure of atrophy than the fiber area measurements. Fiber area decreases and fiber density increases in F animals were quantitatively comparable to those in soleus and extensor digitorum longus after 7 days of weightless flight in Spacelab 3. Our results suggest that VM shows measurable responses to weightlessness.