Myelinated Fibers Research Articles

Optical coherence tomography in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence tomography (OCT) have recently been identified as a potential biomarker for this disease. We aimed to measure circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using OCT and to compare the results in healthy participants with those of individuals having clinically definitive MS with and without a history of optic neuritis. This cross-sectional study recruited patients with clinically confirmed MS, with and without optic neuritis, and healthy individuals as a control group. We documented demographic characteristics, duration of MS, and time elapsed since the episode of optic neuritis. All participants underwent a thorough ocular examination and measurement of total, superior, and inferior cpRNFLT using swept-source OCT. In participants with MS, women outnumbered men in the subsets with (90%) and without (64%) optic neuritis. The control group comprised approximately similar numbers of men and women. There was a statistically significant difference in total, superior, and inferior cpRNFLT between study groups (all P < 0.001). Pairwise comparisons revealed significantly thinner total, superior, and inferior cpRNFLTs in patients having MS with and without (all P < 0.001) optic neuritis when compared with the controls. We found significantly higher total, superior, and inferior cpRNFLTs in women than in men (all P < 0.05). However, we found no significant correlation between total, superior, or inferior cpRNFLT and patient age, duration of MS, or time elapsed since the optic neuritis episode (all P > 0.05), except for a significant moderate inverse correlation between patient age and total cpRNFLT (r = - 0.41; P < 0.05), indicating a loss of total cpRNFLT with age. Patients with clinically confirmed MS, with or without optic neuritis, had a significantly decreased cpRNFLT compared to that of healthy individuals. There was a significant inverse correlation between age and total cpRNFLT and a difference in cpRNFLT between the sexes, indicating that age and sex may influence the measurement of cpRNFLT using OCT in patients with MS. As a screening tool, OCT should be used along with other existing diagnostic modalities for patients with definite or suspected MS. Further longitudinal studies including various classifications of MS with or without isolated episodes of optic neuritis, along with diagnostic accuracy studies, could provide more robust conclusions on the suitability of OCT as a biomarker of MS.

Reverse straatsma syndrome and lamellar cataract: a case report and review of the literature

Myelinated retinal nerve fiber (MRNF) is a developmental anomaly that is often detected during routine ophthalmological examination, but can be an ocular finding in a wide variety of diseases. An important example of this group is the Straatsma Syndrome. Straatsma Syndrome is an entity that presents with the triad of myopia, amblyopia, and MRNF. When this triad is accompanied by hyperopia instead of myopia, it is referred to as the Reverse Straatsma Syndrome. Here, we present a case of Reverse Straatsma Syndrome accompanied by lamellar congenital cataracts.

Non-Invasive High-Resolution Imaging of In Vivo Human Myelinated Axons

This work aims to reveal the microscopic (2–3 micrometer resolution) appearance of human myelinated nerve fibers in vivo for the first time. We analyzed the myelinated retinal nerve fibers of a male patient without other neurological disorders in a non-invasive way using the transscleral optical phase imaging method with adaptive optics. We also analyzed the fellow eye with non-myelinated nerve fibers and compared the results with traditional ocular imaging methods such as optical coherence tomography. We documented the microscopic appearance of human myelin and myelinated axons in vivo. This method allowed us to obtain better details than through traditional ocular imaging methods. We hope these findings will be useful to the scientific community to evaluate neuro-retinal structures through new imaging techniques and more accurately document nerve anatomy and the pathophysiology of this disease.

Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction.

Early-onset fetal growth restriction (FGR) is associated with adverse outcomes. We hypothesised that maternal melatonin administration will improve fetal brain structure in FGR. Surgery was performed on twin-bearing ewes at 88 days (0.6 gestation), and FGR induced in one twin via single umbilical artery ligation. Melatonin was administered intravenously (6 mg/day) to a group of ewes commencing on day of surgery until 127 days (0.85 gestation), when the ewe/fetuses were euthanized, and fetal brains collected. Study groups were control (n = 5), FGR (n = 5), control+melatonin (control+MLT; n = 6) and FGR+melatonin (FGR + MLT; n = 6). Melatonin administration did not significantly alter fetal body or brain weights. Myelin (CNPase+) fibre density was reduced in FGR vs. control animals in most brain regions examined (p < 0.05) and melatonin treatment restored CNPase fibre density. Similar but less pronounced effect was seen with mature myelin (MBP+) staining. Significant differences in activated microglia (Iba-1) activity were seen between lamb groups (MLT mitigated FGR effect) in periventricular white matter, subventricular zone and external capsule (p < 0.05). Similar effects were seen in astrogliosis (GFAP) in intragyral white matter and cortex. Maternal melatonin administration in early onset FGR led to improved myelination of white matter brain regions, possibly mediated by decreased inflammation. Maternal melatonin administration might lead to neuroprotection in the growth-restricted fetus, possibly via dampening neuroinflammation and enhancing myelination. This preclinical study adds to the body of work on this topic, and informs clinical translation. Neuroprotection likely to improve long-term outcomes of this vulnerable infant group.

Unilateral Myelinated Retinal Nerve Fibers Associated with Ipsilateral Myopia, Amblyopia and Exotropia

This report describes a case of unilateral myelinated retinal nerve fibers associated with ipsilateral myopia, amblyopia and exotropia. A 3-year-old boy presented with the complaint of diminished vision in his right eye. Visual acuity testing with a picture at a distance of 2.5 m revealed 1.5 in the left eye, but right visual acuity was not available. Near visual acuity with dot cards was 0.2 in the right eye and 0.6 in the left eye. The refractive error was -7.25D and +1.50D in the right and left eyes, respectively. Fundus examination revealed extensive myelinated retinal nerve fibers in the right eye, but no abnormal findings in the left eye. The axial length was 24.10 mm and 22.90 mm in the right and left eyes, respectively. Cycloplegic retinoscopy revealed a refractive error of a −7.00D in the right eye and plane in the left eye. Glasses with full optical correction were prescribed, and the patient was evaluated one month later, presenting a best-corrected visual acuity of 0.6 in the right eye and 2.0 in the left eye with a picture at a distance of 2.5 m. Three months later, his visual acuity was 0.7 in the right eye. At this point, amblyopia treatment was started with two hours daily of left eye occlusion. One year following the initial presentation, his visual acuity improved 0.8 in the right eye. The type of fixation, the initial visual acuity, the high myopia and the high anisometropia indicated a most likely bad prognosis. However, the age of diagnosis and wearing status of glasses were advantage for treatment effect in this case. Even though this condition is associated with poor visual prognosis, intensive occlusion therapy should always be attempted, along with the prescription of a cycloplegic refraction, due to unexpected and variable responses to treatment.

Magnetic fibrin nanofiber hydrogel delivering iron oxide magnetic nanoparticles promotes peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms.

The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin-angiotensin-aldosterone system, and promotion of β-cell sensitivity to insulin. The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Proximal and Distal Nerve Conduction Studies in Carpal Tunnel Syndrome

Introduction/Aims: The exact reason for the decrease in median nerve motor conduction velocity (MMCV) in the forearm in carpal tunnel syndrome (CTS) is debatable. However, some studies support the hypothesis of blockage of large, myelinated fibers in the carpal tunnel, and/or retrograde axonal degeneration. We aimed to determine the decrease in the MMCV of the second lumbrical (FMMCVL) and abductor pollicis brevis (APB) muscles recorded in the forearm (FMMCVAPB) in patients with CTS compared with a control group and also to compare the MMCV among CTS subgroups with different severity. Methods: The study included data on the hands of 51 patients and 20 volunteer controls. Patients were divided into four groups according to the severity of the involvement, minimal, mild, moderate, and severe. Routine median, ulnar, and comparative conduction studies were performed. By stimulating the median nerve at the palm, wrist, and elbow, responses were recorded over the APB and second lumbrical muscles. MMCV was assessed in the transcarpal segment (TCMMCV) and forearm. Results: The mean FMMCVAPB and FMMCVL in patients were 53.8 ± 4.2 m/s and 54.3 ± 5.6 m/s, respectively, and were significantly slower than in the controls (P &lt; 0.001 and P = 0.012, respectively). The FMMCVL was significantly decreased in the severe group compared with the other three groups (P &lt; 0.001). FMMCVL and FMMCVAPB relatively decreased as CTS severity increased. Conclusion: In this study, FMMCVAPB and FMMCVL were found significantly slower. Slowing of FMMCVL in the forearm is related to the severity of CTS. The decrease in MMCV in the forearm did not parallel the decrease in TCMMCV. This suggests that retrograde axonal degeneration may be the contributing factor to forearm slowing. There is also an association between axonal degeneration and disease severity.

Effects of continuous and pulsed radiofrequency applied for 120 and 240 seconds to rats' sciatic nerve.

Radiofrequency (RF) has been used for many years for pain treatment. The effects of RF on nerves and the underlying mechanism of these effects are not clearly understood. The aim of this study is to show the effects of Pulsed (P-RF) and Continuous (C-RF) RF in light and electron microscopy, and to determine the differences between them. In this study, a total of 60 Rattus norvegicus rats were used in 6 groups. No procedure was performed on the control group. In the Sham group, the electrodes were placed but no current was applied. P-RF for 120 seconds, P-RF for 240 seconds, C-RF for 120 seconds, and C-RF for 240 seconds at 42 °C were applied respectively to the other groups. Sections obtained from sciatic nerves were examined with light and electron microscopy. Examinations of the Sham, P120, and C120 groups were normal. In P240, some morphological changes were observed, but when all samples were examined, these abnormalities were evaluated as negligible. In C240, severe deformation of both myelinated and non-myelinated nerve fibers was observed under an electron and light microscope. Dramatic structural deformities in Schwann cells were observed. P120, P240, and C120 treatments did not produce any deformities in the sciatic nerve. The application of C-RF for 240 seconds produced pathological alterations in the nerve structure.

Nerve Preparation and Recordings for Pharmacological Tests of Sensory and Nociceptive Fiber Conduction Ex Vivo.

Measuring signal propagation through nerves is a classical electrophysiological technique established decades ago to evaluate sensory and motor functions in the nervous system. The whole-nerve preparation provides a valuable model to investigate nerve function ex vivo; however, it requires specific knowledge to ensure successful and stable measurements. Although the methodology for sciatic nerve recordings has long existed, a method for reliable and long-lasting recordings from myelinated and non-myelinated (nociceptive) fibers still needs to be adapted for pharmacological testing. This protocol takes benefits from epineurium sheath removal for pharmacological tests and provides a detailed description of how to make accurate nerve preparations, from the dissection and handling of nerves to epineurium cleaning, fabrication of adaptable suction electrodes for appropriate fiber stimulation and recordings, setting of electrophysiological protocols for compound action potential (CAP) recordings to distinguish between myelinated and non-myelinated (nociceptive) fibers, and finally to the analysis of the datasets of CAP components. We also demonstrate the feasibility of CAP recordings from individual branches in epineurium-free nerve preparations and provide clues to help retain nerve viability and maintain stable recordings over time. Although a sciatic nerve preparation was used here, the methodology can be applied to other nerve-type preparations. Key features • Detailed and simplified protocol for peripheral nerve preparation for recording sensory inputs ex vivo. • Recordings from myelinated and non-myelinated (nociceptive) fibers can be performed hours after nerve preparation. • The protocol involves the epineurium removal to facilitate drug permeability into nerve tissue for pharmacological tests. • The protocol allows physiological and pathological studies (pain/chronic pain conditions).

Familial myelinated nerve fiber

Abstract We describe three cases of myelinated retinal nerve fibres, in a patient, her brother and mother, suggesting that an inherited defect may be responsible in certain cases.

AI‐based studies using fundus images

The artificial intelligence (AI)/deep learning (DL) algorithms were shown to detect diseases based on image analysis, including retinal diseases from fundus photos and optical coherence tomography (OCT) scans, lung diseases from chest radiographs, and skin disorders from skin photos. It was also shown that retinal photos can be used to identify risk factors related with cardiovascular disorders, including blood pressure, smoking and body mass index.The fundus picture was shown to source data for developing AI/DL algorithms detecting many ophthalmic diseases and pathologies, including diabetic retinopathy, diabetic macular edema, retinal artery and vein occlusion, macular hole, epiretinal membrane, AMD, glaucoma, retinopathy of prematurity, myopia, myopic macular degeneration, hyperopia, optic disc edema, optic nerve atrophy, central serous retinopathy, myelinated nerve fibres, and retinitis pigmentosa. Moreover, fundus pictures were also used to develop many AI/DL algorithms detecting non ophthalmic diseases and pathologies, including Alzheimer and Parkinson disease, risk of stroke, risk of cardiac infarction, systemic hypertension, chronic renal disease, peripheral arterial disease, and anaemia.

Electromagnetic stimulation in diaphragm dysfunction: repetitive peripheral magnetic stimulation as a method of choice during the rehabilitation period after stroke. (Literature review)

To perform a review and comparison of modern methods of electromagnetic stimulation of the diaphragm; to determine the role of repetitive peripheral magnetic stimulation (rPMS) in the diaphragm dysfunction as a result of stroke. An analysis of publications from the Pubmed and Elibrary databases for 2008-2024 years was conducted. The search was done by the following keywords: diaphragm dysfunction, repetitive peripheral magnetic stimulation of phrenic nerve, stroke, hemiparesis. There is a real possibility of effective diaphragm stimulation for recovery of its function due to the innervation of the diaphragm strictly by the phrenic nerves, their large diameter, presence of myelinated fibers as well as anatomical location of the phrenic nerves. Direct electric stimulation of the phrenic nerve is usually applied in the case of long-term continuous support of respiratory function. Non-invasive techniques of electric or magnetic stimulation of the phrenic nerve or directly of the diaphragmatic muscle are used in the case of temporary respiratory support or recovery of diaphragm function. The motor neurons of the brain and peripheral nerves are activated, thus a peak strength of the variable magnetic field usually reachs 1-2 T in rPMS. Application of rPMS affects the efferent nerve fibers, causing muscle contractions, and activates sensory afferent fibers, creating a stimulating effect on the superjacent nervous structures. It is advisable to use rPMS of the phrenic nerve in the cervical segment or rPMS of one of the segments of the diaphragmatic muscle in the case of unilateral diaphragm lesion during the recovery period after stroke. It is important to consider the frequency of exposure in the 10-30 Hz range, the closest location of the coil to the stimulation area, the choice of the coil shape depending on the localization when adjusting parameters of rPMS. The use of rPMS of the phrenic nerve and diaphragm allows to preserve and recover motor and contractile functions of the diaphragm in different pathological conditions, including its unilateral lesion as a result of stroke. The method of rPMS of the phrenic nerves has a number of advantages over electric stimulation and repetitive transcranial magnetic stimulation, since it allows to achieve an effective motor response with less intensity of exposure, is painless and non-contact, better tolerated by patients.

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.

Episodic Neurological Dysfunction in X-Linked Charcot-Marie-Tooth Disease: Expansion of the Phenotypic and Genetic Spectrum.

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2-45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

A Fresh Cadaver Study on the Innervation of Brachioradialis and Extensor Carpi Radialis Longus Muscles

Distal nerve transfers have revolutionized peripheral nerve surgery by allowing the transfer of healthy motor nerves to paralyzed ones without causing additional morbidity. Radial nerve branches to the brachialis (Ba), brachioradialis (Br), and extensor carpi radialis longus (ECRL) muscles have not been investigated in fresh cadavers. The radial nerve and its branches were dissected in 34 upper limbs from 17 fresh cadavers. Measurements were taken to determine the number, origin, length, and diameter of the branches. Myelinated fiber counts were obtained through histological analysis. The first branch of the radial nerve at the elbow was to the Ba muscle, followed by the branches to the Br and ECRL muscles. The Ba and Br muscles consistently received single innervation. The ECRL muscle showed varying innervation patterns, with one, two, or three branches. The branches to the Br muscles originated from the anterior side of the radial nerve, whereas the branches to the Ba and ECRL muscles originated from the posterior side. The average myelinated fiber counts favored the nerve to Br muscle over that to the ECRL muscle, with counts of 542 versus 350 and 568 versus 302 observed in hematoxylin and eosin and neurofilament staining, respectively. This study provides detailed anatomical insights into the motor branches of the radial nerve to the Ba, Br, and ECRL muscles. Understanding the anatomy of the radial nerve branches at the elbow is of utmost importance when devising a reconstructive strategy for upper limb paralysis. These findings can guide surgeons in selecting appropriate donor or recipient nerves for nerve transfer in cases of high tetraplegia and lower-type brachial plexus injuries.

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.

Neuroprotective effect of 2-ethyl-6-methyl-3-hydroxypyridine succinate on the sciatic nerve and its segmental centers in experimental paclitaxel-induced peripheral neuropathy

Up to 60 % of patients suffer from the neurotoxicity of the chemotherapy drug Paclitaxel, namely paclitaxel-induced peripheral neuropathy (PIPN), during the treatment of breast cancer, ovarian cancer, and non-small cell lung cancer. Of these, up to 25 % of patients require modification of the paclitaxel treatment regimen, including dose reduction, delay, or discontinuation of therapy. Previous attempts to use neuroprotective agents in humans and in animal models have not shown sufficient efficacy in preventing or significantly reducing the manifestations of PIPN. The aim of our study was to study the effect of the neuroprotective agent 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) on the morpho-functional parameters of the sciatic nerve and its segmental centers in experimental PIPN. In the experiment, 56 white rats were used, which were injected intraperitoneally with Paclitaxel at a dose of 2 mg/kg of body weight 4 times after one day, after which the animals were divided into an experimental group – 24 animals that were injected with HS and a control group (24 animals, injection of water for injections). The method of studying mechanical allodynia was von Frey monofilaments, thermal hyperalgesia was studied by the hot plate test, and the electron microscopic examination was carried out according to generally accepted methods and studied with the help of a PEM-125 K electron microscope. The results of the hot plate test and the use of von Frey monofilaments showed that the use of HS reliably reduces manifestations of PIPN on the 7th, 14th and 28th days of the experiment. In rats treated with HS, destructive-dystrophic phenomena in the myelin nerve fibers of the sciatic nerve are less pronounced, and in individual fibers in the axon, phenomena of incomplete splitting of mitochondria with the formation of vacuoles filled with medium electron density contents are observed, and small young mitochondria are also visualized. During the first 28 days, we noted less pronounced destructive-dystrophic changes in the neurons of the spinal cord nodes, namely: chromatolysis of light and dark neurons and swelling of their cytoplasm, phenomena of neuronophagy in gliocytes, hypertrophy of certain areas of the myelin sheath. The results of the electron microscopic study are fully consistent with the data of neurophysiological studies and indicate the possibility of using HS as an effective neuroprotector in PIPN.

Chitosan nerve conduit filled with ZIF-8-functionalized guide microfibres enhances nerve regeneration and sensory function recovery in sciatic nerve defects

Nerve conduits have shown promise as alternatives to autologous nerves, but their repair effects need to be improved. The topographical guidance and functionalization of scaffolds are crucial in nerve repair. In this work, a chitosan-based nerve graft filled with guiding fibres modified by ZIF-8 nanoparticles (CS@ZIF-8) was fabricated for defective nerve repair. An in vitro study demonstrated that CS@ZIF-8 exhibited excellent cytocompatibility and could significantly promote Schwann cell proliferation. In vivo, nerve conduits filled with CS@ZIF-8 were observed to guide stronger axonal longitudinal elongation. Rats bridged with the conduit filled with CS@ZIF-8 showed significant morphological and functional improvements in terms of regenerated nerve density, the number of myelinated nerve fibres, the number of myelin layers, the thickness of myelin sheath, target muscle recovery and sensory function compared to those transplanted with the hollow conduit and the conduit filled with pure chitosan fibres. The repair effects achieved by using the conduit filled with CS@ZIF-8 were similar to those of autografts. Altogether, the data here show that nerve conduits filled with ZIF-8-loaded guide fibres provide a promising approach for repairing nerve defects.

Drug and Toxin-Induced Cerebellar Ataxias

Ataxia is the inability to coordinate voluntary movement and can present with a variety of symptoms involving dyscoordination of gait and extremity movement, slurred speech, and abnormal eye movements. Ataxia can be divided into either cerebellar or sensory. Cerebellar ataxia originates from damage to the cerebellum or its connecting tracts, while sensory ataxia is a result of damage to the afferent sensory pathways such as the dorsal column and large myelinated proprioceptive fibers