Density Of Myelinated Fibers Research Articles

Hypertension is associated with the reduction in epidermal small fibres independently of sural nerve inflammation in type 2 diabetic subjects.

Diabetic polyneuropathy (DPN) is a multifactorial disease associated not only with hyperglycaemia but also with circulatory disturbances such as hypertension. A close interaction between the immune system and hypertension is known. It remains unclear whether the inflammatory response is associated with hypertension in the pathology of human DPN. Autopsied patients were evaluated: 7 non-diabetic patients (nDM), 11 non-diabetic patients with hypertension (nDMHT), 6 patients with diabetes (DM) and 9 patients with hypertension and diabetes (DMHT). Intraepidermal nerve fibre density (IENFD) was examined by immunofluorescent staining. Dissected sural nerve (SNs) were morphometrically quantified. Dermal and endoneurial macrophage infiltration was evaluated by double immunostaining using anti-CD68 and anti-CD206 antibodies. IENFD was significantly decreased in DM compared to nDM (p < 0.05) and was further decreased in DMHT (p < 0.05). Myelinated nerve fibre density (MNFD) in the SN was significantly decreased in DM compared with nDM (p < 0.05) and further decreased in DMHT (p < 0.01 vs. DM). The infiltration of CD206-/CD68+ proinflammatory macrophages in the SN was significantly increased in DM compared to nDM (p < 0.05), whilst the number of CD206+/CD68+ anti-inflammatory macrophages was decreased in DM (p < 0.05). Hypertension had no impact on macrophage infiltration. The ratio of CD206- and CD206+ macrophage was negatively correlated with MNFD (r = 0.42, p < 0.05) but not IENFD (r = 0.30, p = 0.09). Dermal CD206+ macrophage infiltration was similar amongst all groups. Diabetes complicated by hypertension significantly increased the total diffusion barrier thickness (p < 0.01 vs. DM). Total diffusion barrier thickness was inversely correlated with both IENFD (r = -0.59, p < 0.01) and MNFD (r =-0.62, p < 0.01). Our results suggest that vascular factors and inflammation might be synergistically involved in pathological changes in human diabetic patients through different mechanisms.

Repetitive magnetic stimulation prevents dorsal root ganglion neuron death and enhances nerve regeneration in a sciatic nerve injury rat model

Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.

Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.

Adolescent binge ethanol impacts H3K9me3-occupancy at synaptic genes and the regulation of oligodendrocyte development.

Binge drinking in adolescence can disrupt myelination and cause brain structural changes that persist into adulthood. Alcohol consumption at a younger age increases the susceptibility of these changes. Animal models to understand ethanol's actions on myelin and white matter show that adolescent binge ethanol can alter the developmental trajectory of oligodendrocytes, myelin structure, and myelin fiber density. Oligodendrocyte differentiation is epigenetically regulated by H3K9 trimethylation (H3K9me3). Prior studies have shown that adolescent binge ethanol dysregulates H3K9 methylation and decreases H3K9-related gene expression in the PFC. Here, we assessed ethanol-induced changes to H3K9me3 occupancy at genomic loci in the developing adolescent PFC. We further assessed ethanol-induced changes at the transcription level with qPCR time course approaches in oligodendrocyte-enriched cells to assess changes in oligodendrocyte progenitor and oligodendrocytes specifically. Adolescent binge ethanol altered H3K9me3 regulation of synaptic-related genes and genes specific for glutamate and potassium channels in a sex-specific manner. In PFC tissue, we found an early change in gene expression in transcription factors associated with oligodendrocyte differentiation that may lead to the later significant decrease in myelin-related gene expression. This effect appeared stronger in males. Further exploration in oligodendrocyte cell enrichment time course and dose response studies could suggest lasting dysregulation of oligodendrocyte maturation at the transcriptional level. Overall, these studies suggest that binge ethanol may impede oligodendrocyte differentiation required for ongoing myelin development in the PFC by altering H3K9me3 occupancy at synaptic-related genes. We identify potential genes that may be contributing to adolescent binge ethanol-related myelin loss.

Influence of shortwave laser therapy on morphometric parameters of sciatic nerve regeneration after experimental neurorrhaphy

The aim of this work was to reveal the effectiveness of delayed laser therapy for the regeneration of the sciatic nerve. Materials and methods. In 21 rats, transection and epineural microsurgical suture of the right sciatic nerve (SN) were performed. In 16 rats (experimental group) in the period from 1.0 to 2.5 months after surgery, a course of laser therapy (LT-1, n = 8) and a delayed (after 6 months) course of laser therapy (LT-2, n = 8) were used 18 sessions were performed in each subgroup. Laser therapy was not performed in 5 operated animals and they were included in the control group. The terms of withdrawal of rats from the experiment were 2.5 and 12.0 months after the operation. During the morphometry of semi-thin sections distal to the level of the sutures, the volumetric density of the constituent elements of the SN, the number density of myelinated nerve fibers (MNF), their diameters, the thickness of the axons and myelin sheath, the myelination index (index G) distribution of MNF by diameter and dependence of index G on the fiber caliber were measured. For double control, we used muscle morphometry data from intact rats (Intact). Muscle tissue was additionally examined by the method of transmission electron microscopy using a generally accepted technique with a REM-100 electron microscope (Selmi, Sumy, Ukraine). Results. In the control group, as compared to the intact group, the numerical density of muscle fibers was 21 % higher, but 38 % less than the numerical density of microvessels, therefore, the vascularization index was reduced by 1.7 times. The obtained results indicated laser compensation for denervation atrophy, which was confirmed by morphometric data. Conclusions. The results of the study indicate a stimulating prolonged effect of delayed laser therapy in regenerative axonogenesis.

Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.

Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified. This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR-A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC-1) culture to examine the direct effect of TTR-A97S protein on endothelial cells. In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC-1 culture in which the expression of collagen IV was upregulated after exposure to TTR-A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p-selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv. Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration.

Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls.

Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 (T1D) and type 2 diabetes (T2D). No cure for DPN is available, but several potential targets have been proposed for treatment. Heat shock proteins (HSPs) are known to respond to both hyper- and hypoglycemia. DPN can be diagnosed using electrophysiology and studied using peripheral nerve biopsies. This study aimed to analyze the presence and patterns of HSPs in peripheral nerve biopsies from subjects with T1D, T2D, and healthy controls. Posterior interosseous nerves (PIN) from a total of 56 subjects with T1D (n = 9), with T2D (n = 24), and without diabetes (i.e., healthy controls, n = 23) were harvested under local anesthesia and prepared for quantitative mass spectrometry analysis. Protein intensities were associated with electrophysiology data of the ulnar nerve and morphometry of the same PIN, and differences in protein intensities between groups were analyzed. In total, 32 different HSPs were identified and quantified in the nerve specimens. No statistically significant differences were observed regarding protein intensities between groups. Furthermore, protein intensities did not correlate with amplitude or conduction velocity in the ulnar nerve or with the myelinated nerve fiber density of PIN. Quantitative proteomics can be used to study HSPs in nerve biopsies, but no clear differences in protein quantities were observed between groups in this cohort.

322-OR: Proinflammatory Macrophage Infiltration in Sural Nerve Is Associated with Reduction of Myelinated Nerve Fiber Density but Not IENFD in Human Diabetic Subjects

Background: The etiology of diabetic polyneuropathy (DPN) is multifactorial, and other than hyperglycemia, circulatory disturbance such as hypertension can be involved. Pro-inflammatory macrophages (M1) infiltration in the peripheral nerve is known to be the pathogenesis of DPN. However, it is still unclear how the inflammation and circulatory disturbance are involved in the pathological changes of human DPN. Methods: Autopsied cases at Hirosaki University Hospital were evaluated: 7 nondiabetic cases (nDM), 11 nondiabetic cases with hypertension (nDM+HT), 6 diabetes cases (DM), 9 cases with hypertension and diabetes (DM+HT). Intraepidermal nerve fiber density (IENFD) was examined by immunofluorescent staining with the skin tissue 10 cm above external condyle. Dissected sural nerves were pathologically examined. Macrophage infiltration into the endoneurium of sural nerves was evaluated by double immunostaining using anti-CD68 and anti-CD163 antibodies. Results: HbA1c level was significantly higher in DM and DM+HT than in nDM (p&amp;lt;0.01, respectively). IENFD was significantly decreased in DM compared to nDM (p&amp;lt;0.05) and further decreased in DM+HT (p&amp;lt;0.05 vs DM). The infiltration of M1 was significantly increased in DM (p&amp;lt;0.05). M1 infiltration was comparable between DM and DM+HT. Regression analysis showed that the M1/anti-inflammatory macrophages (M2) ratio was not significantly correlated with IENFD (r=0.3, p=0.09). Morphometric measurements of the sural nerve using semithin sections revealed that myelinated nerve fiber density (MNFD) was significantly decreased in DM compared with nDM (p&amp;lt;0.05). MNFD was comparable between DM and DM+HT. MNFD was inversely correlated with M1/M2 ratio (r=0.37, p&amp;lt;0.05). Conclusions: Our results suggest that the factors other than sural nerve inflammation, such as hypertension, are possibly more involved in the loss of IENFD in DPN. Disclosure H. Mizukami: None. S. Osonoi: None. Y. Takeuchi: None. T. Sasaki: None.

Experimental unilateral intracerebral hemorrhage induces delayed bilateral neurodegeneration of sciatic nerve fibres in rats.

Pathological processes, such as inflammatory effects, oxidative stress, apoptosis and cytotoxicity of blood after an intracerebral hemorrhage (ICH), generally contribute to a secondary injury. One of the secondary ICH consequences in the nervous system may be delayed neurodegeneration of the peripheral nerves. Therefore, the aim of our study was to investigate possible structural changes in the sciatic nerve and changes in the conduction velocity via this nerve at different terms after experimental ICH in male Wistar rats. Intracerebral hemorrhage was provided by direct injection of autologous blood into the capsula interna. On the 10th day after ICH mean conduction velocity in sciatic nerve was 15% smaller compared to the control. On the 30th and 90th days after ICH, highly significant decreases in the conduction velocity by 62% and 60%, respectively in comparison with the control group of animals were observed. The data of morphometric analysis demonstrated significant decreases in the mean diameter and density of myelinated fibres at all examined terms after ICH. A number of the myelin sheaths were swollen and lost their regular laminations. Axoplasmic and myelin degenerations were the most frequent events in these nerve fibres; reductions of the diameter of the axis cylinders were also observed. In the contralateral nerve (related to the hemisphere with ICH), negative changes were greater, while the ipsilateral nerve was also subjected to those. Our data demonstrate that the consequences of unilateral ICH in the capsula interna induce bilateral negative changes in the peripheral nervous system of rats.

CIDP/autoimmune nodopathies with nephropathy: a case series study.

The co-morbidity of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)/autoimmune nodopathies with nephropathy has been gradually known in recent years. This study was intended to explore the clinical, serological and neuropathological features of seven patients with CIDP/autoimmune nodopathies and nephropathy. Among 83 CIDP patients, seven were identified with nephropathy. Their clinical, electrophysiological and laboratory examination data were collected. The nodal/paranodal antibodies were tested. The sural biopsies were performed in all the patients, and renal biopsies were operated in 6 patients. Six patients had chronic onsets and one had an acute onset. Four patients exhibited peripheral neuropathy preceding nephropathy while two showed concurrent onset of neuropathy and nephropathy, and one started with nephropathy. All the patients showed demyelination in electrophysiological examination. Nerve biopsies showed mild to moderate mixed neuropathies including demyelinating and axonal changes in all patients. Renal biopsies showed membranous nephropathy in all 6 patients. Immunotherapy was effective in all patients, with two patients showing good response to corticosteroid treatment alone. Four of the patients were positive to anti-CNTN1 antibody. Compared with anti-CNTN1 antibody-negative patients, antibody-positive patients had a higher proportion of ataxia (3/4 vs. 1/3), autonomic dysfunction (3/4 vs. 1/3), less frequent antecedent infections (1/4 vs. 2/3), higher cerebrospinal fluid proteins (3.2g/L vs. 1.69 g/L), more frequent conduction block on electrophysiological examination (3/4 vs. 1/3), higher myelinated nerve fiber density, and positive CNTN1 expression in the glomeruli of kidney tissues. Anti-CNTN1 antibody was the most frequent antibody in this group of patients with CIDP/autoimmune nodopathies and nephropathy. Our study suggested that there might be some clinical and pathological differences between the antibody positive and negative patients.

Ultrasound Therapy of Injury Site Modulates Gene and Protein Expressions in the Dorsal Root Ganglion in a Sciatic Nerve Crush Injury Rat Model.

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury.

Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension.

Persistent arterial hypertension initiates cardiac autonomic imbalance and alters cardiac tissues. Previous studies have shown that neural component contributes to arterial hypertension etiology, maintenance, and progression and leads to brain damage, peripheral neuropathy, and remodeling of intrinsic cardiac neural plexus. Recently, significant structural changes of the intracardiac neural plexus were demonstrated in young prehypertensive and adult hypertensive spontaneously hypertensive rats (SHR), yet structural alterations of intracardiac neural plexus that occur in the aged SHR remain undetermined. Thus, we analyzed the impact of uncontrolled arterial hypertension in old (48-52 weeks) SHR and the age-matched Wistar-Kyoto rats (WKY). Intrinsic cardiac neural plexus was examined using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in cardiac sections and whole-mount preparations. Our findings demonstrate that structural changes of intrinsic cardiac neural plexus caused by arterial hypertension are heterogeneous and may support recent physiological implications about cardiac denervation occurring together with the hyperinnervation of the SHR heart. We conclude that arterial hypertension leads to (i) the decrease of the neuronal body area, the thickness of atrial nerves, the number of myelinated nerve fibers, unmyelinated axon area and cumulative axon area in the nerve, and the density of myocardial nerve fibers, and (ii) the increase in myelinated nerve fiber area and density of neuronal bodies within epicardiac ganglia. Despite neuropathic alterations of myelinated fibers were exposed within intracardiac nerves of both groups, SHR and WKY, we consider that the determined significant changes in structure of intrinsic cardiac neural plexus were predisposed by arterial hypertension.

Clinical and biochemical characterization of hereditary transthyretin amyloidosis caused by E61K mutation.

Objects: This study was intended to find out more about the clinical characterizations of patients carrying transthyretin (TTR) E61K (p.Glu81Lys) gene mutation and the biochemical characterization of this mutant protein.Materials and methods: Five patients who had been diagnosed with hereditary transthyretin amyloidosis and two asymptomatic carriers carrying TTR E61K gene mutation were reported. Biochemical and biophysical tests were conducted to observe the thermodynamic and kinetic stability. Fibril formation tests measured by turbidity assay were performed to explore the pathogenicity of this mutation. Kinetic stabilizer responsiveness was measured to determine the inhibitory effect on protein aggregation.Results: The average age of onset for the five patients was 62 years, and the course of the disease ranged from 2 to 10 years. Cardiac disease was prominent in this group of patients. Nerve pathology revealed a mildly to moderately reduced myelinated fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment. E61K-TTR was characterized as a kinetically destabilized protein compared to WT-TTR but its thermodynamic stability was not compromised. In addition, the subunit exchange of E61K with WT-TTR further destabilized the heterozygous tetramer. Meanwhile, the E61K:WT heterozygous tetramer exhibited a poor response to kinetic stabilizers in the fibril formation assay. Finally, the serum TTR tetramer concentration was low in E61K-TTR symptomatic patients and in one asymptomatic gene carrier. Vyndamax (Tafamidis) could increase the TTR tetramer concentration.Conclusions: Patients with E61K mutation tended to be late-onset. The concentration of TTR tetramer in the serum might serve as a biomarker to monitor disease progress, therapeutic window time, and therapeutic response to TTR kinetic stabilizer drugs.

Clinical feature and sural biopsy study in nitrous oxide-induced peripheral neuropathy.

ObjectiveThe objective was to analyze the clinical characteristics and pathological characteristics of sural biopsy in nitrous oxide (N2O) -induced peripheral neuropathy.MethodsWe recruited 18 patients with N2O abuse-induced neurological disorders and reported their demographic data, clinical manifestations, laboratory examinations, and nerve conduction studies. Seven patients underwent sural nerve biopsy pathologic examination.ResultsAll 18 patients had polyneuropathy, the nerve conduction results showed significant reductions in motor and sensory amplitudes, slowing of conduction velocities, and prolongation of latencies in most tested nerves compared to the controls. Toluidine blue staining of semi-thin sections of sural nerve biopsy showed decreased myelinated nerve fiber density, increased thin myelinated nerve fiber density, and axonal regeneration. Electron microscopy showed axonal degeneration and nerve regeneration.ConclusionThe main manifestations of peripheral nerve damage caused by the abuse of N2O are lower limb weakness and distal sensory disorder. The nerve conduction study results demonstrated that mixed axonal and demyelinating neuropathy was the most common type of neuropathy. Sural biopsy showed the main pathological change was chronic axonal degeneration.

Morphological study of the phrenic nerve to determine a reference value for the myelinated fiber density in elderly individuals.

Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi-thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 μm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 μm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals.

Morphological and morphometric study of the superior vestibular nerve trunk in guinea pigs.

The guinea pig has been chosen as a research model for otologic or neuropathic studies due to the relative ease of the cochlea, cochlear nerve, and vestibular nerve dissection. Little data have been reported on the normality of these nerves. The vestibular nerve is composed of the superior vestibular, inferior vestibular, and branch nerves. This study aimed to study the microscopic anatomy of the superior vestibular nerve (SVN) of guinea pigs using light microscopy and to search for normality patterns for use in experimental models in basic otologic research. We used eight male albino guinea pigs (Cavia porcellus, English strain), weighing between 400 and 500 g. After anesthetizing, the animals were perfused with a fixative solution of 2.5% glutaraldehyde. Dissection was performed by the access method to the temporal bone, coming to the rock and exposing the cochlea and vestibular nerve. The NVS fragments were removed, postfixed in osmium tetroxide, and embedded in the epoxy plastic resin Poly/Bed 812® (Polysciences Inc., Warrington, PA). Semi-thin transverse serial sections (0.5μm) were made using a microtome MT6000-XL, RMC, Inc. and stained with toluidine blue. Morphology and morphometry were described and evaluated using the KS 400 application (Kontron 2.0, EchingBei, Munich, Germany) by macro, a computer program specially designed and developed for the study of the VIII nerve. The SVN was found to be devoid of epineurium, with only a thin conjunctive tissue layer. The myelin sheath of guinea pigs is relatively thin compared to the sensory and motor nerves found in mammals. The average fascicular area SVN was 0.19 ± 0.05 mm2 , with the largest area found to be 0.24 mm2 and the lowest was 0.12 mm2 . The average number of fibers was 5,753.00 ± 538 fibers. The density of myelinated fibers reached 32,316.08 ± 11,375.29 fibers/mm2 . Its diameter ranged from 1.0 to 9μm and its peak was 3μm. The measured results confirm the results of another study, indicating that the methodology is appropriate and reproducible. These findings are important for the evaluation of injured nerves in experimental models of peripheral neuropathy and basic ear disease.

Prospect of Stem Cells as Promising Therapy for Brachial Plexus Injury: A Systematic Review.

BackgroundBrachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength.Study DesignSystematic Review; Level of evidence V.Data SourcesA systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms (“stem cell”) AND (“brachial plexus”) as search keywords.MethodsThe process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes.ResultsIn total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury.ConclusionThis review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.

HP49 : Severity of carpal tunnel syndrom in case of diabetes : A comparative study

To estimate the degree of severity of CTS in hands of diabetic patients in comparison with non-diabetic patients. Introduction : Carpal tunnel syndrom (CTS) is the most common mononeuropathy in which diabetes is a risk factor. Methods : It’s a retrospective study of one month collecting patients with hands’ paresthesia. G1 represents the diabetic group and G2 the non-diabetic group. A nerve conduction study (NCS) of both nerves median and ulnar was done, evaluating the sensory and motor functions. The ulnar nerve’s NCS was normal in both groups. The severity of CTS was classified in normal, sensory, or both sensory and motor injury. Pearson test was used. Results : 36 patient (G1=18 and G2=18) were matched in age: G1 had a mean age 56±9,2 and G2 50,6±7,1 year-old. There was a statistically predominance of sensory injury in G2 and a statistically predominance of both injuries (sensory and motor) in G1 with p= 0,04. Discussion : It appears that in CTS of diabetic patients no exposed to hand work, density of myelinated nervous fibers and capillars would be reduced. Inflammatory cytokines and vascular growth factors would be in origin of disturbance of microvascular circulation leading to a demyelination and axonal degeneration, explaining why G1 had more severe stages than G2. Conclusion : Diabetes is not the only risk factor of CTS but it would be an accelerator of its aggravation consequently to the metabolic dysfunction.

Comparison of the vitality tests used in the dental clinical practice and histological analysis of the dental pulp.

In dentistry, indirect diagnostic methods such as electrical sensibility testing and pulse oximetry are used to assess the status of the pulp. Our study aimed to determine the correlation between hemoglobin oxygen saturation and vascular volume density (Vvasc). We also wanted to examine an electrical sensibility test and the volume density of myelinated nerve fibers (Vnerv). Twenty-six intact permanent premolars were included in the study. For histological analysis, the pulp tissue was stained with hematoxylin-eosin and immunohistochemically for von Willebrand factor and S100 to detect blood vessels and myelinated nerve fibers, respectively. The stereological analysis was used to determine the Vvasc and Vnerv. Statistical analysis was done using the Pearson correlation test and Welch’s ANOVA test. Histological analysis showed that the pulp tissue was strongly vascularized and innervated. A significant positive correlation was found between Vvasc and hemoglobin oxygen saturation levels (p = 0.030). A significant negative correlation was found between Vnerv and the lowest electrical voltage that patient felt (p = 0.033). According to the maturity of the dental apex, teeth were divided into a group with open (n = 6, OA group) and closed apex (n = 20, CA group). We found that pulps in the CA group had higher Vnerv than the OA group (p = 0.037). In contrast, there were no significant differences in Vvasc of the pulp tissue (p = 0.059), oxygen saturation (p = 0.907), or electrical voltage (p = 0.113) between both groups. We can conclude that the measurement of pulse oximetry and electrical sensibility test reflects the morphology of healthy pulp tissue independently of the maturity of the dental apex.

TTR Gly83Arg Mutation: Beyond Familial Vitreous Amyloidosis.

BackgroundGly83Arg variation is a type of TTR mutation specific to the Chinese population. Patients of hereditary transthyretin amyloidosis (ATTR) with Gly83Arg variation predominantly present with blurred vision and most of these cases are reported by ophthalmologists. There is currently no systematic assessment of extraocular features of ATTR with Gly83Arg variation.MethodsSix patients and two asymptomatic carriers with molecularly confirmed Gly83Arg variation of ATTR from three unrelated families were identified by sequencing the TTR gene. The clinical, electrophysiological, ultrasonic, and pathological data were collected and analyzed.ResultsThis study included six patients and two carriers with TTR Gly83Arg mutation, all of whom came from the Han nationality of China. The average age of onset for the six patients was 39 years, and the course of disease ranged from 5 to 19 years. All the patients started with blurred vision, which was diagnosed as vitreous opacity (VO). Most of the patients developed sensory-motor polyneuropathies over years or even more than a decade (4–15 years) after VO. However, the heterogeneity of peripheral neuropathies among these patients remained large between families. Autonomic impairment also occurred after VO, with varying degrees of abnormalities seen in the associated autonomic assessments. None of the patients had any symptoms of cardiac impairment, but abnormal results were found in examinations. A combined biopsy of the sural nerve and muscle was also performed. Nerve pathology revealed the moderately reduced myelinated nerve fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment.ConclusionsThis is a detailed account of Gly83Arg mutation-related ATTR, focusing on the extraocular presentations of this special variant in Chinese. Clinical features of this variant are early-onset, ocular involvement predominance, neurological, and cardiac involvement along with the disease, and relatively long survival.