Nerve Fiber Damage Research Articles

Activation of type II cannabinoid receptors as variant for mesenchymal stem cell potentiation in a model of peripheral neuropathic pain

Transplantation of adipose-derived mesenchymal stem cells (ADMSCs) is currently considered as one of the treatment methods of peripheral neuropathic pain. The analgesic effect of ADMSCs has been proven, and one of the potential options for its enhancement and prolongation could be the activation of type 2 cannabinoid receptors (CB2 receptors). The antinociceptive and reparative effects of ADMSCs were analyzed after type 2 cannabinoid receptors (CB2) pharmacological stimulation by the selective agonist AM1241 on the ADMSC’s membranes and in the tissues of the area of sciatic nerve traumatic injury in rats. It was found that pharmacological stimulation of CB2 receptors on ADMSC’s membranes accelerated the recovery of nociceptive sensitivity to mechanical and thermal stimuli compared with transplantation of ADMSCs alone. Early (before transplantation of ADMSCs) activation of CB2 receptors in tissues surrounding the sciatic nerve more effectively attenuated nociceptive responses to thermal stimuli in the long-term period of the experiment. Stimulation of CB2 receptors did not significantly affect the rate of recovery of gait parameters in rats after ADMSCs transplantation, but led to the structure recovery of the sciatic nerve distal segment of rats. The latter was expressed in increased proliferation of Schwann cells and a decrease in the number of damaged nerve fibers.

Identification of small diameter nerve fiber damage in hemodialysis patients' hands using the cutaneous silent period

BackgroundThe arteriovenous fistula is the most effective vascular access option for hemodialysis patients. An important and largely unreported concern detected at follow-up is the complaints of tingling or numbness in the hands of those patients. Furthermore, the cutaneous silent period qualifies as a straightforward evaluation of small nerve fiber function. This study aims to evaluate the function of small-diameter nerve fibers in the hands of patients undergoing continuous hemodialysis (HD) on the side with the arteriovenous fistula (AVF) and on the contralateral side.ResultsA cross-sectional study of 40 randomly chosen patients with chronic kidney disease on regular hemodialysis three times weekly the cutaneous silent period (CSP) was recorded on the hand with and without AV fistula. The cutaneous silent period (CSP) CSP was elicited by electrical square pulse stimulation using standard bipolar electrodes. The average cutaneous silent period onset and end latencies demonstrated significant prolongation in the hemodialysis patient group (arteriovenous fistula and non-arteriovenous fistula) compared with the control group. Correlation between cutaneous silent period with hemodialysis duration and adequacy of hemodialysis (KT\\V). There was a statistically negative correlation observed between cutaneous silent period onset latency on the arteriovenous side and a positive correlation with KT\\V on non-arteriovenous fistula. side.ConclusionsHemodialysis patients recommended to undergo regular neurophysiological testing to check for small nerve fiber affection. In particular, measuring the cutaneous Silent period that provides a quick and noninvasive way to rule out small A-delta nerve malfunction. In addition, less nerve injury results from hemodialysis's increased efficiency.

Establishment of a facial nerve trunk crush injury model and evaluation of facial nerve self-healing in rats.

To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.

Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury.

Over the years, electroconductive hydrogels (ECHs) have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury (PNI) with diabetes, given their favorable mechanical and electrical properties identical to endogenous nerve tissue. Nevertheless, PNI causes the loss of locomotor function and inflammatory pain, especially in diabetic patients. It has been established that bone marrow stem cells-derived exosomes (BMSCs-Exos) have analgesic, anti-inflammatory and tissue regeneration properties. Herein, we designed an ECH loaded with BMSCs-Exos (ECH-Exos) electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief. Given its potent adhesive and self-healing properties, this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure, avoiding the cumbersome implantation process. Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells. Meanwhile, Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway, thereby attenuating inflammatory pain in diabetic PNI. Additionally, ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo, consequently ameliorating muscle denervation atrophy and further promoting functional restoration. Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration, functional restoration and pain relief in patients with diabetic PNI.

Autonomic Small-Fiber Pathology in Patients With Fibromyalgia

In this clinical and skin biopsy study, we aimed to investigate whether fibromyalgia-associated small-fiber pathology (SFP), consisting of an intraepidermal nerve fiber loss, implies damage of dermal autonomic nerve fibers and how this damage is associated with autonomic symptoms that patients with fibromyalgia syndrome experience. Using skin biopsy, we investigated intraepidermal nerve fiber density, piloerector muscle, and sweat gland nerve fiber density (SGNFD) in 138 participants, that is, 58 patients with fibromyalgia syndrome, 48 healthy subjects, and 32 patients with small-fiber neuropathy. In patients with fibromyalgia-associated SFP, we also investigated how the different skin biopsy variables correlated with autonomic symptoms, as assessed with the Composite Autonomic Symptom Score 31 questionnaire. We found that in patients with fibromyalgia-associated SFP, the piloerector muscle and SGNFD were lower than that in healthy subjects. However, the autonomic small-fiber damage had no correlation with autonomic symptoms severity. In patients with SFP, the intraepidermal, piloerector muscle, and SGNFD were higher than that in patients with small-fiber neuropathy. Our clinical and skin biopsy study shows that patients with fibromyalgia have a reduction of dermal autonomic small fibers paralleling the intraepidermal nerve fiber loss, thus indicating that SFP also implies autonomic small nerve fiber damage. However, the autonomic small-fiber damage we found had no correlation with the severity of autonomic symptoms, and thus its clinical impact is still undetermined. PerspectiveIn patients with fibromyalgia, SFP also affects autonomic fibers. These novel data provide additional insights into the pathophysiology of fibromyalgia syndrome, highlighting the complex role of small-fiber damage in the clinical picture of fibromyalgia.

Contemporary Interpretations of Ophthalmological Manifestations of Chronic Myeloproliferative Neoplasms

The course of chronic myeloproliferative neoplasms (CMPN), a group of systemic hematological diseases, can be accompanied by various complications and changes in tissues and organs of the whole organism. The eye is the only organ where damage of nerve fibers and blood vessels can be directly observed and examined, and ocular symptoms can be the initial, manifest of systemic pathology, the toxic effects of modern targeted therapy, or the first manifestation of a relapse of the disease after treatment. The most frequently described manifestations are caused by hematological anomalies that cause microvascular disorders. Such changes today remain insufficiently studied in terms of the using new research methods and contemporary targeted therapy. In addition, ocular symptoms may precede more serious extraocular complications. Combined ophthalmological and hematological examination of patients with CMPN can become a preventive approach for early diagnosis and timely treatment.

Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition.

This study aimed to determine whether lipopolysaccharide (LPS) induces the loss of corneal nerve fibers in cultured trigeminal ganglion (TG) cells, and the underlying mechanism of LPS-induced TG neurite damage. TG neurons were isolated from C57BL/6 mice, and the cell viability and purity were maintained for up to 7 days. Then, they were treated with LPS (1 µg/mL) or the autophagy regulator (autophibib and rapamycin) alone or in combination for 48 h, and the length of neurites in TG cells was examined by the immunofluorescence staining of the neuron-specific protein β3-tubulin. Afterwards, the molecular mechanisms by which LPS induces TG neuron damage were explored. The immunofluorescence staining revealed that the average length of neurites in TG cells significantly decreased after LPS treatment. Importantly, LPS induced the impairment of autophagic flux in TG cells, which was evidenced by the increase in the accumulation of LC3 and p62 proteins. The pharmacological inhibition of autophagy by autophinib dramatically reduced the length of TG neurites. However, the rapamycin-induced activation of autophagy significantly lessened the effect of LPS on the degeneration of TG neurites. LPS-induced autophagy inhibition contributes to the loss of TG neurites.

Corneal confocal microscopy reveals small nerve fibre loss correlating with motor function in adult spinal muscular atrophy.

5q Spinal muscular atrophy (SMA) is a progressive, inherited, and severely disabling - yet treatable - motor neuron disease. Although treatment options have evolved in recent years, biomarkers for treatment monitoring and prognosis prediction remain elusive. Here, we investigated the utility of corneal confocal microscopy (CCM), a non-invasive imaging technique to quantify small corneal nerve fibres in vivo, as a diagnostic tool in adult SMA. In this cross-sectional study, 19 patients with SMA type 3 and 19 healthy controls underwent CCM to measure corneal nerve fibre density (CNFD), corneal nerve fibre length (CNFL), and corneal nerve branch density (CNBD), as well as corneal immune cell infiltration. Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores and a 6-Minute Walk Test (6MWT) were conducted to explore any correlation between CCM findings and motor function. Corneal nerve fibre parameters were decreased in SMA patients versus healthy controls (CNFD: p = 0.030; CNFL: p = 0.013; CNBD: p = 0.020) in the absence of relevant immune cell infiltration. CNFD and CNFL correlated with HFMSE scores (CNFD: r = 0.492, p = 0.038; CNFL: r = 0.484, p = 0.042) and distance covered in the 6MWT (CNFD: r = 0.502, p = 0.042; CNFL: r = 0.553, p = 0.023). Corneal confocal microscopy CCM reveals sensory neurodegeneration in SMA, thereby supporting a multisystem view of the disorder. Subclinical small nerve fibre damage correlated with motor function. Thus, CCM may be ideally suited for treatment monitoring and prognosis.

Corneal Confocal Microscopy Demonstrates No Evidence of Small Nerve Fiber Pathology in Obese Children and Adolescents (P2-9.008)

<h3>Objective:</h3> To assess for evidence of small nerve fiber pathology in obese children and adolescents using corneal confocal microscopy (CCM). <h3>Background:</h3> The global prevalence of obesity among children and adolescents has increased dramatically over the past few decades, and childhood obesity has become a significant public health concern. Studies have shown an increased prevalence of neuropathic symptoms in obese children indicating small nerve fiber pathology. We have previously used corneal confocal microscopy (CCM), a rapid, non-invasive ophthalmic technique, to show corneal nerve fiber loss in adults with painful diabetic neuropathy, adults with obesity and children with type 1 diabetes. <h3>Design/Methods:</h3> Twenty obese children and adolescents (age 14.0 ± 2.51 years, BMI 37.27 ± 7.14 kg/m²) and 20 healthy controls (age 12.83 ± 1.91 years, BMI 22.27 ± 5.47 kg/m²) underwent vibration perception threshold (VPT) assessment and CCM to quantify corneal nerve fiber density (CNFD) (no./mm²), corneal nerve branch density (CNBD) (no./mm²) and corneal nerve fiber length (CNFL) (mm/mm²). Obese children also underwent body composition analysis using TANITA to assess body fat percentage. <h3>Results:</h3> Obese children had a normal VPT (3.20 ± 0.95 vs. controls). There was a non-significant trend for a lower CNFD (19.01 ± 5.2 vs. 21.91 ± 4.6; P=0.06), but no difference in CNBD (33.02 (26.13–42.04) vs. 35.04 (29.46–5134); P=0.25) or CNFL (14.5 ± 2.6 vs. 14.4 ± 2.1; P=0.89) in obese children compared to healthy controls. There was no correlation between CNFD (P=0.643), CNBD (P=0.950) and CNFL (P=0.598) with body fat percentage. <h3>Conclusions:</h3> There is no evidence of abnormal vibration perception or small nerve fiber damage in obese children and adolescents. <b>Disclosure:</b> Ms. Wahbeh has nothing to disclose. Hoda Gad has nothing to disclose. Mrs. Elgassim has nothing to disclose. The institution of Ioannis Petropoulos has received research support from GBS CIDP Foundation International . Georgios Ponirakis has nothing to disclose. Prof. Hussain has nothing to disclose. Prof. Malik has nothing to disclose.

Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis

BackgroundHereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, but life-threatening protein misfolding disorder due to TTR gene mutations. Cardiomyopathy (ATTRv-CM) and polyneuropathy (ATTRv-PN) with early small nerve fibre involvement are the most common manifestations. Timely diagnosis and treatment initiation are key to limiting progression of disease. Corneal confocal microscopy (CCM) is a non-invasive method to quantify corneal small nerve fibres and immune cell infiltrates in vivo.MethodsThis cross-sectional study investigated the utility of CCM in 20 patients with ATTRv amyloidosis (ATTRv-CM, n = 6; ATTRv-PN, n = 14) and presymptomatic carriers (n = 5) compared to 20 age- and sex-matched healthy controls. Corneal nerve fibre density, corneal nerve fibre length, corneal nerve branch density, and cell infiltrates were assessed.ResultsCorneal nerve fibre density and nerve fibre length were significantly lower in patients with ATTRv amyloidosis compared to healthy controls regardless of the clinical phenotype (ATTRv-CM, ATTRv-PN) and corneal nerve fibre density was significantly lower in presymptomatic carriers. Immune cell infiltrates were only evident in patients with ATTRv amyloidosis, which correlated with reduced corneal nerve fibre density.ConclusionsCCM identifies small nerve fibre damage in presymptomatic carriers and symptomatic patients with ATTRv amyloidosis and may serve as a predictive surrogate marker to identify individuals at risk of developing symptomatic amyloidosis. Furthermore, increased corneal cell infiltration suggests an immune-mediated mechanism in the pathogenesis of amyloid neuropathy.

Immunohistochemical Study of Macrophages of Sciatic Rat Nerve after Damage and Subperineural Injection of Mesenchymal Stem Cells

The dynamics of the processes of Wallerian degeneration in the Wistar-Kyoto rat sciatic nerve after injury (ligation, 40 s) was studied.The density of Iba-1+ macrophages and the state of myelin fibers stained with Luxol strong blue in the distal segment of the nerve at different times after injury were studied. Parts of rats were subperineurally transplanted with MSCs from the bone marrow of Wistar-Kyoto rats. It was shown that the highest distribution density of macrophages in the distal segment of the nerve was observed 7 days after surgery. The use of cell therapy leads to a decrease in the number of macrophages during this period and to a delay in the demyelination of damaged nerve fibers. Sixty days after the operation, the macrophage population density and the number of remyelinated regenerating nerve fibers of the distal nerve segment did not differ in control (ligature) and experimental (ligature and MSC injection) animals. The molecular mechanisms of the noted changes in the early stages after injury require further research.

Acute Treatment with the M-Channel (Kv7, KCNQ) Opener Retigabine Reduces the Long-Term Effects of Repetitive Blast Traumatic Brain Injuries.

We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleusto the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of theEGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.

Features of polyneuropathy in diabetes mellitus and chronic alcoholism

This article discusses the features of the pathogenesis and symptoms of two of the most common causes of polyneuropathy. On the one hand, the alcoholic genesis of nerve fiber damage is discussed - we will consider how chronic alcoholism provokes the appearance of polyneuropathy. On the other hand, an equally important and frequent inducer of a decrease in all types of sensitivity in patients is diabetes mellitus. Moreover, in some cases, polyneuropathy can occur even before the establishment of diabetes mellitus as a causal diagnosis. Thus, we see the need to highlight important aspects of pathogenesis, and, despite the differences in the development of both processes, the commonality of symptoms.

Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol

Background and Objective: Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. Materials and Methods: A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks. Pain tolerance thresholds of hind paws toward thermal and mechanical stimuli were assessed. Expressions of PGP9.5, P2X3, CGRP, and TRPV-1 targeting afferent nerve fibers in hind paw skin and glial cells in the spinal dorsal horn were examined via immunohistochemistry and immunofluorescence. Results: Oral cilostazol ameliorated the symptoms of mechanical allodynia but not thermal analgesia in DM rats. Significant reductions in PGP9.5-, P2X3-, CGRP, and TRPV-1-labeled penetrating nerve fibers in the epidermal layer indicated denervation of sensory nerves in the hind paw epidermis of DM rats. Denervation significantly improved in groups that received Cilo30 and Cilo100 in a dose-dependent manner. Cilostazol administration also suppressed microglial hyperactivation and increased astrocyte expressions in spinal dorsal horns. Conclusions: Oral cilostazol ameliorated hyperglycemia-induced peripheral small nerve fiber damage in the periphery of diabetic rats and effectively mitigated diabetic neuropathic pain via a central sensitization mechanism. Our findings present cilostazol not only as an effective option for managing symptoms of neuropathy but also for deterring the development of diabetic neuropathy in the early phase of type I diabetes.

Diagnostic Accuracy of Perception Threshold Tracking in the Detection of Small Fiber Damage in Type 1 Diabetes.

An objective assessment of small nerve fibers is key to the early detection of diabetic peripheral neuropathy (DPN). This study investigates the diagnostic accuracy of a novel perception threshold tracking technique in detecting small nerve fiber damage. Participants with type 1 diabetes (T1DM) without DPN (n = 20), with DPN (n = 20), with painful DPN (n = 20) and 20 healthy controls (HCs) underwent perception threshold tracking on the foot and corneal confocal microscopy. Diagnostic accuracy of perception threshold tracking compared to corneal confocal microscopy was analyzed using logistic regression. The rheobase, corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) (all P < .001) differed between groups. The diagnostic accuracy of perception threshold tracking (rheobase) was excellent for identifying small nerve fiber damage, especially for CNFL with a sensitivity of 94%, specificity 94%, positive predictive value 97%, and negative predictive value 89%. There was a significant correlation between rheobase with CNFD, CNBD, CNFL, and Michigan Neuropathy Screening Instrument (all P < .001). Perception threshold tracking had a very high diagnostic agreement with corneal confocal microscopy for detecting small nerve fiber loss and may have clinical utility for assessing small nerve fiber damage and hence early DPN. NCT04078516.

Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury.

Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague-Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups (n = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.

A Retinex-based variational model for noise suppression and nonuniform illumination correction in corneal confocal microscopy images

Objective. Corneal confocal microscopy (CCM) image analysis is a non-invasive in vivo clinical technique that can quantify corneal nerve fiber damage. However, the acquired CCM images are often accompanied by speckle noise and nonuniform illumination, which seriously affects the analysis and diagnosis of the diseases. Approach. In this paper, first we propose a variational Retinex model for the inhomogeneity correction and noise removal of CCM images. In this model, the Beppo Levi space is introduced to constrain the smoothness of the illumination layer for the first time, and the fractional order differential is adopted as the regularization term to constrain reflectance layer. Then, a denoising regularization term is also constructed with Block Matching 3D (BM3D) to suppress noise. Finally, by adjusting the uneven illumination layer, we obtain the final results. Second, an image quality evaluation metric is proposed to evaluate the illumination uniformity of images objectively. Main results. To demonstrate the effectiveness of our method, the proposed method is tested on 628 low-quality CCM images from the CORN-2 dataset. Extensive experiments show the proposed method outperforms the other four related methods in terms of noise removal and uneven illumination suppression. Significance This demonstrates that the proposed method may be helpful for the diagnostics and analysis of eye diseases.

Comparative analysis of neurofilament light chain levels in the serum and cerebrospinal fluid in rats subjected to partial sciatic nerve ligation.

Neurofilament light chain (NfL) has recently been used as a biomarker of neurodegeneration. Although cerebrospinal fluid (CSF) NfL levels are hypothesized to affect blood NfL levels, whether blood NfL levels change independently of the CSF during peripheral nerve injury remains unclear. Thus, we evaluated the nervous tissues histopathology and serum and CSF NfL levels in partial sciatic nerve-ligated rats at 6 h and one, three, or seven days after the surgery. Sciatic and tibial nerve fiber damage was observed at 6 h after the surgery, and peaked at three days postoperatively. The serum NfL levels peaked 6 h to one day after ligation, but they tended to return to the normal seven days after ligation. However, the CSF NfL levels were unchanged throughout the study period. In conclusion, the comparative evaluation of serum and CSF NfL levels can provide useful information as biomarkers of nerve tissue damage and its distribution.

The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.

Enrichment of nervonic acid in Acer truncatum Bunge oil by combination of two-stage molecular distillation, one-stage urea complexation and five-stage solvent crystallization

Nervonic acid is the world's first and only potent substance that can repair damaged nerve fibers and promote nerve cell regeneration with high nutritional value. The wide variety of fatty acids in plant oils and fats with similar structures makes the large-scale separation and purification of high-purity nervonic acid very difficult. A new combined process of molecular distillation, urea inclusion and solvent crystallization was established to prepare high-purity nervonic acid with the mixed fatty acids obtained after saponification and acidification of Acer truncatum Bunge oil as raw materials. First, according to the difference in the mean free path of fatty acids, molecular distillation was used to separate and remove C16 saturated fatty acid of palmitic acid and four C18–C20 fatty acids of stearic, oleic, linoleic, and linolenic acids. The content of C16–C20 fatty acids decreased from 72.92% to 19.22% after two-stage molecular distillation processes, in which the contents of saturated fatty acid of palmitic acid decreased to about 0.5%. Then, according to the difference in carbon chain length and saturation of fatty acid, the contents of C22–C24 saturated fatty acids of tetracosanoic and docosanoic acids decreased to 0.21% and 0.07% by urea inclusion with urea/free fatty acid preparation by saponification (SPOMFs) ratio as 0.6. In addition, all saturated fatty acids were basically separated. Finally, according to the difference in the solubility of fatty acids in solvents, the C18–C20 unsaturated fatty acids of oleic, linoleic, and linolenic acids and C22 unsaturated fatty acid of erucic acid were removed by solvent crystallization. The content of C18–C20 unsaturated fatty acids decreased to less than 5% with pentanol as the solvent after the first stage solvent crystallization. The content of erucic acid decreased to 3.47% with anhydrous ethanol as the solvent after the second to fifth stage solvent crystallization. The combined process of molecular distillation, urea inclusion and low temperature crystallization innovatively adopted an efficient, simple and easy-to-industrial solvent crystallization method to separate erucic and nervonic acids, obtaining nervonic acid with purity of 96.53% and final yield of 47.99%.