Higher G-ratio Research Articles

Long-term demyelination and aging-associated changes in mice corpus callosum; evidence for the role of accelerated aging in remyelination failure in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder affecting the central nervous system. Evidence suggests that age-related neurodegeneration contributes to disability progression during the chronic stages of MS. Aging is characterized by decreased regeneration potential and impaired myelin repair in the brain. It is hypothesized that accelerated cellular aging contributes to the functional decline associated with neurodegenerative diseases. We assessed the impact of aging on myelin content in the corpus callosum (CC) and compared aging with the long-term demyelination (LTD) consequents induced by 12 weeks of feeding with a cuprizone (CPZ) diet. Initially, evaluating myelin content in 2-, 6-, and 18-month-old mice revealed a reduction in myelin content, particularly at 18 months. Myelin thickness was decreased and the g-ratio increased in aged mice. Although a lower myelin content and higher g-ratio were observed in LTD model mice, compared to the normally aged mice, both aging and LTD exhibited relatively similar myelin ultrastructure. Our findings provide evidence that LTD exhibits the hallmarks of aging such as elevated expression of senescence-associated genes, mitochondrial dysfunction, and high level of oxidative stress as observed following normal aging. We also investigated the senescence-associated β-galactosidase activity in O4+ late oligodendrocyte progenitor cells (OPCs). The senescent O4+/β-galactosidase+ cells were elevated in the CPZ diet. Our data showed that the myelin degeneration in CC occurs throughout the lifespan, and LTD induced by CPZ accelerates the aging process which may explain the impairment of myelin repair in patients with progressive MS.

Ral GTPases are critical regulators of spinal cord myelination and homeostasis.

Efficient myelination supports nerve conduction and axonal health throughout life. In the central nervous system, oligodendrocytes (OLs) carry out this demanding anabolic duty in part through biosynthetic pathways controlled by mTOR. We identify Ral GTPases as critical regulators of mouse spinal cord myelination and myelin maintenance. Ablation of Ral GTPases (RalA, RalB) in OL-lineage cells impairs timely onset and radial growth of developmental myelination, accompanied by increased endosomal/lysosomal abundance. Further examinations, including transcriptomic analyses of Ral-deficient OLs, were consistent with mTORC1-related deficits. However, deletion of the mTOR signaling-repressor Pten in Ral-deficient OL-lineage cells is unable to rescue mTORC1 activation or developmental myelination deficiencies. Induced deletion of Ral GTPases in OLs of adult mice results in late-onset myelination defects and tissue degeneration. Together, our data indicate critical roles for Ral GTPases to promote developmental spinal cord myelination, to ensure accurate mTORC1 signaling, and to protect the healthy state of myelin-axon units over time.

Persistent myelin abnormalities in a third trimester-equivalent mouse model of fetal alcohol spectrum disorder.

Abnormal diffusion within white matter (WM) tracts has been linked to cognitive impairment in children with fetal alcohol spectrum disorder. Whether changes to myelin organization and structure underlie the observed abnormal diffusion patterns remains unknown. Using a third trimester-equivalent mouse model of alcohol exposure, we previously demonstrated acute loss of oligodendrocyte lineage cells with persistent loss of myelin basic protein and lower fractional anisotropy (FA) in the corpus callosum (CC). Here, we tested whether these WM deficits are accompanied by changes in: (i) axial diffusion (AD) and radial diffusion (RD), (ii) myelin ultrastructure, or (iii) structural components of the node of Ranvier. Mouse pups were exposed to alcohol or air vapor for 4h daily from postnatal day (P)3 to P15 (BEC: 160.4±12.0mg/dl; range=128.2 to 185.6mg/dl). Diffusion tensor imaging (DTI) and histological analyses were performed on brain tissue isolated at P50. Diffusion parameters were measured with Paravision™ 5.1 software (Bruker) following ex vivo scanning in a 7.0T MRI. Nodes of Ranvier were identified using high-resolution confocal imaging of immunofluorescence for Nav 1.6 (nodes) and Caspr (paranodes) and measured using Imaris™ imaging software (Bitplane). Myelin ultrastructure was evaluated by calculating the G-ratio (axonal diameter/myelinated fiber diameter) on images acquired using transmission electron microscopy. Consistent with our previous study, high resolution DTI at P50 showed lower FA in the CC of alcohol-exposed mice (p=0.0014). Here, we show that while AD (diffusion parallel to CC axons) was similar between treatment groups (p=0.30), RD (diffusion perpendicular to CC axons) in alcohol-exposed subjects was significantly higher than in controls (p=0.0087). In the posterior CC, where we identified the highest degree of abnormal diffusion, node of Ranvier length did not differ between treatment groups (p=0.41); however, the G-ratio of myelinated axons was significantly higher in alcohol-exposed animals than controls (p=0.023). High resolution DTI revealed higher RD at P50 in the CC of alcohol-exposed animals, suggesting less myelination of axons, particularly in the posterior regions. In agreement with these findings, ultrastructural analysis of myelinated axons in the posterior CC showed reduced myelin thickness in alcohol-exposed animals, evidenced by a higher G-ratio.

Multiple sclerosis plaques may undergo continuous myelin degradation: a cross-sectional study with myelin and axon-related quantitative magnetic resonance imaging metrics.

We hypothesize that myelin is more susceptible to damage over time than axons. We investigated the association between the estimated duration from the onset of multiple sclerosis (MS) plaques and myelin- and axon-related quantitative synthetic magnetic resonance imaging (SyMRI) and neurite orientation dispersion and density imaging (NODDI) metrics. We analyzed 31 patients with MS with 73 newly appeared plaques. Simple linear regression analysis was performed to assess the association between the estimated duration from the onset of plaques and quantitative MRI metrics. These metrics included the myelin volume fraction (MVF), axon volume fraction, and g-ratio in plaque and normal-appearing white matter. MS plaques with a longer estimated duration from onset were significantly correlated with a lower MVF (slope = - 0.0070, R2 = 0.0970), higher g-ratio (slope = 0.0078, R2 = 0.0842) (all P values < 0.05). These results suggested that myelin in plaques undergoes continuous damage, more so than axons. Myelin imaging with SyMRI and NODDI may be useful for the quantitative assessment of temporal changes in MS plaques.

Research on the pathological mechanisms of nerve decompression in relieving tactile allodynia in diabetic rats

Objectives To explore the pathological mechanism of peripheral nerve decompression in relieving tactile allodynia in diabetic rats. Methods Healthy adult male Sprague Dawley rats were randomly divided into 5 groups for different interventions: group Ⅰ (healthy control, n=10), group Ⅱ (diabetes model, n=20), group Ⅲ (diabetes model with latex tube placement, n=10), group Ⅳ (diabetes model with latex tube placement and nerve decompression, n=10), group V (diabetes model with latex placement and merely operational area exposure, n=10). The diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Nerve decompression was performed by removal of latex tube encircling the sciatic nerve at 3 weeks post model establishment. The paw withdrawal threshold was tested 3 days after modeling with the use of up-down method. Diabetic rats with tactile allodynia in 4 experimental groups (groups Ⅱ-Ⅳ) were preserved. Morphometric analysis of myelinated and non-myelinated nerve fibers was performed with the use of projection electron microscope. Western blot and immunofluorescence were used to localized and determined the expression of GABAB receptor protein in spinal dorsal horn. Results Three weeks after operation, the incidence of tactile allodynia in STZ-induced rats[55.0%(11/20)] was lower than that in diabetic rats with latex tube placement (groups Ⅲ, Ⅳ and Ⅴ) [86.7%(26/30), χ2=6.254, P=0.012]. The paw withdrawal threshold in group Ⅰ (13.41±1.88 g) was higher than those in groups Ⅱ-Ⅳ (4.06±1.28 g, 3.09±1.43 g, 4.02±1.96 g, 4.15±1.87 g respectively, P<0.05). At 5 weeks post operation, the paw withdrawal threshold in group Ⅳ was higher than those of group Ⅱ, Ⅲ and Ⅴ(all P<0.05). When compared with group Ⅰ, smaller myelinated fibers area and density, as well as higher g-ratio were revealed by electron microscope in each experimental group (all P<0.05). Larger myelinated fiber area and density, as well as lower g-ratio were noted in group Ⅳ when compared with those in group Ⅱ and Ⅴ (all P<0.05). The results of western blot showed that lower expression of GABAB receptor was noted in experimental groups (Ⅱ, Ⅲ, Ⅳ and Ⅴ) when compared with group Ⅰ (all P<0.05), and higher expression of GABAB receptor in both NF-200+ areas and neurons of spinal dorsal horn was noted in group Ⅳ when compared with group V (P<0.05) at 3 weeks post nerve decompression. The results of immunofluorescence showed that lower expression of GABAB receptor in both NF-200+ areas and neurons of spinal dorsal horn was noted in experimental groups (Ⅱ, Ⅲ, Ⅳ and Ⅴ) when compared with group Ⅰ (all P<0.05). Conclusions Peripheral nerve decompression can relieve the tactile allodynia of diabetic rats mainly by removing the compression damage of myelinated nerve fibers, lifting the GABAB receptor downregulation-mediated central sensitivity, thereby relieving the pathological state of elevated spinal excitability. Key words: Diabetes mellitus; Disease models, animal; Tactile allodynia; Nerve decompression

The Use of a Hypoallergenic Dermal Matrix for Wrapping in Peripheral Nerve Lesions Regeneration: Functional and Quantitative Morphological Analysis in an Experimental Animal Model.

Introduction The aim of this research was to test, in an animal model, the nerve regeneration technique with a hypoallergenic acellular dermal matrix used to wrap the microsurgical neural suture. Materials and Methods Two groups of rats received the cut of limb right median nerves. The regeneration technique considers for both groups an end-to-end nerve suture. In the experimental group (A) was used also a wrapping protocol by a conduit of collagen matrix currently used in oral surgery. The animals underwent functional grasping tests (at 1, 3, 5, and 7 months) and a histological and quantitative analysis of distal nerve was performed at the end of experimental time. Result After seven months, the grasping test reveals functional recovery in each tested animal; this improvement is more evident in Group A. The fibers appear well organized with restored myelin sheaths in both groups. Group A showed a great quantity of connective tissue surrounding the nerve. The quantitative morphology analysis in both groups shows a similar fibers density, fiber diameter, and myelin thickness. The differences between the groups in axon mean diameter are significant. In Group A M/d, D/d, and g-ratio is significantly higher compared to control group. Conclusions Histological and functional assessments show a functional recovery of the injured nerve in the test groups, stressed by the results of the grasping tests and the meaningful increasing in fiber diameter and higher g-ratio. Moreover, a connective tissue cuff distinguishes the distal portion of the injured nerve. Considering the easy availability and handling of the material used in this study we can conclude that this experimental technique can be considered as a valid alternative to protect nerves in nerve wrap surgery.

Diabetes increases mechanical sensitivity and causes morphological abnormalities in the sural nerve that are prevented by treadmill training

In this investigation we evaluated the effects of treadmill training on mechanical sensitivity and sural nerve morphology in diabetic rats. Rats were divided into 3 groups: control (C); diabetic (D); and trained diabetic (TD). Training was performed for 8 weeks. Mechanical sensitivity was evaluated using von Frey filaments. Sural nerve analysis included fiber area, diameter, density of myelinated fibers, area occupied by connective tissue, myelin sheath thickness, and g-ratio. Animals in the D group had a reduced mechanical sensitivity threshold. Morphometric study showed that the D group had a smaller myelinated fiber area and diameter, higher density of fibers and area occupied by connective tissue, thinner myelin sheath, and higher g-ratio. The D group had a higher percentage of small myelinated fibers and a lower percentage of large-diameter myelinated fibers than the C and TD groups. Training prevents functional and morphological abnormalities in the sural nerve caused by diabetes.

Factors Affecting Grinding Performance with Electroplated CBN Wheels

An experimental investigation was conducted to evaluate the effect of CBN crystal characteristics and plating thickness on the performance of electroplated CBN wheels. Wheels containing tougher CBN crystals generally exhibited less wear and a higher G-ratio, and also required less power. Furthermore, contrary to expectations, less wear and higher G-ratio were also obtained for wheels with a thinner layer of nickel plating despite an increased tendency for large-scale crystal loss. This would indicate that the overall wheel wear depends more on crystal exposure than on active grain density, which could facilitate chip removal and grinding fluid access. Extended grinding tests up to wheel failure ascertain the improved grinding performance with tougher crystals and thinner electroplated layers.

Name order patterns of graduate candidates and supervisors in Chinese publications: A case study of three major Chinese universities

Studying three Chinese major universities of different type, this article attempts to validate earlier results related to authors' name order in papers co-authored by graduate candidates and their supervisors. Candidates for the doctoral degree as well as the master's degree are considered. Defining the g-ratio as the fraction of co-authored publications where the graduate student's name precedes that of the supervisor's we obtain the following results. 1) Generally, master's level g-ratios are smaller than the corresponding doctoral level g-ratios. 2) The three doctoral g-ratio time series have a common characteristic: they tend to a limiting target value of somewhat more than 80%. The master's time series of the three universities extend themselves in parallel with the doctoral time series. 3) The g-ratio of collaborative papers related to the dissertation is higher than the g-ratio of collaborative papers not related to the dissertation. This is true on the doctoral level as well as on the master's level. 4) Different disciplines have different g-ratios, representing disciplinary customs in graduate candidate-supervisor collaboration, the highest g-ratio in the doctoral case occurring in biology (except for Tsinghua University that does not offer courses in biology). 5) There exist only small differences between the g-ratios of different kinds of universities. 6) In recent years, the same candidate-supervisor collaboration patterns exist in international publications as in domestic ones. The fact that the doctoral g-ratios of all three universities are as high as 80% reflects a universal regularity in the structure of scientific collaboration between doctoral candidates and their supervisors in China.

上向き単粒研削法による超砥粒の評価

An overcut fly-milling test with inclined workpiece has been made to accurately evaluate the chipping and wear characteristics of superhard abrasive grains (diamond, CBN) on various hard materials. The Al2O3 and SiC grains were also tested for comparison. The milling experiment was carried out on a surface grinder at a speed of 38 m/s and a feed of 4.0 m/min. The maximum depth of cut was 110 μm. The test was conducted both in dry and wet. The work materials used are hardened SUJ 2, cemented carbide, sintered alumina, etc. Thus, a quantitative evaluation of the chipping and attritious wear was made for each grain by tracing across the grooves with stylus instrument. The data obtained has been treated statistically. The CBN grain proved to be the most resisting to the chipping and attritious wear for the cutting of SUJ 2 steel, and hence, has the highest G-ratio. But, this grain has no ability to cut the cemented carbide or the ceramics used. As far as the diamond grain is concerned, the lowest G-ratio was obtained in the grinding of cemented carbide, followed by sintered Si3N4, and the highest G-ratio was obtained on grinding silicon. The supply of grinding fluid leads to finer chipping and higher chipping probability.

単粒チッピング破壊実験における研削比について

In the earlier study the wear and metal removal in single grain wear test have been investigated on many grain-work combinations. On the other hand, a series of plain fly milling test have been made to evaluate the resistance of grain to micro-chipping on the same grains and works, but in this research the metal removal, or G-ratio, has never estimated. In the present paper the numerical results of the G-ratio are presented, which were obtained based on the previous experimental data on micro-chipping characteristic, provided that grain is a sphere. The ratio was determined as a function of depth of cut. From the result of G-ratio, the rating and the compatibility of grain to work have been discussed. The results obtained are summarized as follows : The G-ratio is seen to increase at first with depth of cut and reach a maximum at a depth of cut of 20 to 40μm. The maximum G-ratio ranges from 400 to 7000 in compliance with grain and work material. Specially, the grain type appears to much effective on the G-ratio. Roughly speaking, it is evident that the grain types of having high hardness and medium toughness, such as the 40 SH, the SH or the R 71 grains, have higher G-ratio than the highly friable grain types, the WA or the 2 A grains, and also highly soft grain, the AZ 40 grain, with the exception of the SUS 27 steel, where the tougher grain indicates higher G-ratio.